In biology , cell signaling ( cell signalling in British English ) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes .
157-502: A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse . The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell . Neurotransmitters are released from synaptic vesicles into the synaptic cleft where they are able to interact with neurotransmitter receptors on the target cell. Some neurotransmitters are also stored in large dense core vesicles . The neurotransmitter's effect on
314-540: A withdrawal state with emotional-motivational deficits upon cessation of cocaine use. Crack baby is a term for a child born to a mother who used crack cocaine during her pregnancy. The threat that cocaine use during pregnancy poses to the fetus is now considered exaggerated. Studies show that prenatal cocaine exposure (independent of other effects such as, for example, alcohol, tobacco, or physical environment) has no appreciable effect on childhood growth and development. In 2007, he National Institute on Drug Abuse of
471-411: A 'divide and conquer' approach to finding the structure of the proteins (crystallising each domain separately). The function of such receptors located at synapses is to convert the chemical signal of presynaptically released neurotransmitter directly and very quickly into a postsynaptic electrical signal. Many LICs are additionally modulated by allosteric ligands , by channel blockers , ions , or
628-399: A binding site for a different protein and thus induce protein–protein interaction. In this case, the ligand (called epidermal growth factor , or EGF) binds to the receptor (called EGFR ). This activates the receptor to phosphorylate itself. The phosphorylated receptor binds to an adaptor protein ( GRB2 ), which couples the signal to further downstream signaling processes. For example, one of
785-426: A bridge between the use of different groups of drugs. It is legal for people to use coca leaves in some Andean nations, such as Peru and Bolivia, where they are chewed, consumed in the form of tea, or are sometimes incorporated into food products. Coca leaves are typically mixed with an alkaline substance (such as lime ) and chewed into a wad that is retained in the buccal pouch (mouth between gum and cheek, much
942-400: A catalytic function; and a single transmembrane helix . The signaling molecule binds to the receptor on the outside of the cell and causes a conformational change on the catalytic function located on the receptor inside the cell. Examples of the enzymatic activity include: Intracellular receptors exist freely in the cytoplasm, nucleus, or can be bound to organelles or membranes. For example,
1099-445: A cell surface receptor that is part of an ion channel . GABA binding to a GABA A receptor on a neuron opens a chloride -selective ion channel that is part of the receptor. GABA A receptor activation allows negatively charged chloride ions to move into the neuron, which inhibits the ability of the neuron to produce action potentials . However, for many cell surface receptors, ligand-receptor interactions are not directly linked to
1256-447: A few seconds. The most prevalent transmitter is glutamate , which is excitatory at well over 90% of the synapses in the human brain. The next most prevalent is gamma-Aminobutyric Acid, or GABA, which is inhibitory at more than 90% of the synapses that do not use glutamate. Although other transmitters are used in fewer synapses, they may be very important functionally: the great majority of psychoactive drugs exert their effects by altering
1413-517: A flat, hard surface (such as a mobile phone screen, mirror, CD case or book) and divided into "bumps", "lines" or "rails", and then insufflated. A 2001 study reported that the sharing of straws used to "snort" cocaine can spread blood diseases such as hepatitis C . Subjective effects not commonly shared with other methods of administration include a ringing in the ears moments after injection (usually when over 120 milligrams) lasting 2 to 5 minutes including tinnitus and audio distortion. This
1570-411: A greater likelihood of relapse when the drug is withheld. ΔFosB increases the expression of AMPA receptor subunit GluR2 and also decreases expression of dynorphin , thereby enhancing sensitivity to reward. DNA damage is increased in the brain of rodents by administration of cocaine. During DNA repair of such damages, persistent chromatin alterations may occur such as methylation of DNA or
1727-455: A group of DNA binding proteins. Upon binding, the receptor-ligand complex translocates to the nucleus where they can alter patterns of gene expression. Steroid hormone receptors are found in the nucleus , cytosol , and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which lead to changes in gene expression over
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#17330863237161884-480: A hypothesis that cocaine may also function as a so-called "DAT inverse agonist" or "negative allosteric modifier of DAT" resulting in dopamine transporter reversal , and subsequent dopamine release into the synaptic cleft from the axon terminal in a manner similar to but distinct from amphetamines . Sigma receptors are affected by cocaine, as cocaine functions as a sigma ligand agonist. Further specific receptors it has been demonstrated to function on are NMDA and
2041-431: A joint or blunt . Acute exposure to cocaine has many effects on humans, including euphoria, increases in heart rate and blood pressure, and increases in cortisol secretion from the adrenal gland. In humans with acute exposure followed by continuous exposure to cocaine at a constant blood concentration, the acute tolerance to the chronotropic cardiac effects of cocaine begins after about 10 minutes, while acute tolerance to
2198-435: A ligand activated gate function. When these receptors are activated, they may allow or block passage of specific ions across the cell membrane. Most receptors activated by physical stimuli such as pressure or temperature belongs to this category. G-protein receptors are multimeric proteins embedded within the plasma membrane. These receptors have extracellular, trans-membrane and intracellular domains. The extracellular domain
2355-438: A ligand. Reducing the sensitivity of the receptor is a result of receptors being occupied for a long time. This results in a receptor adaptation in which the receptor no longer responds to the signaling molecule. Many receptors have the ability to change in response to ligand concentration. When binding to the signaling molecule, the receptor protein changes in some way and starts the process of transduction, which can occur in
2512-477: A long period of time who do not hydrate sufficiently may experience demineralization of their teeth due to the pH of the tooth surface dropping too low (below 5.5). Cocaine use also promotes the formation of blood clots . This increase in blood clot formation is attributed to cocaine-associated increases in the activity of plasminogen activator inhibitor , and an increase in the number, activation, and aggregation of platelets . Chronic intranasal usage can degrade
2669-473: A marked elevation of blood pressure, which can be life-threatening, abnormal heart rhythms , and death. Anxiety, paranoia , and restlessness can also occur, especially during the comedown. With excessive dosage, tremors, convulsions and increased body temperature are observed. Severe cardiac adverse events, particularly sudden cardiac death , become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels. Incidental exposure of
2826-401: A modulatory effect. Purine neurotransmitters, like ATP , are derived from nucleic acids. Metabolic products such as nitric oxide and carbon monoxide have also been reported to act like neurotransmitters. Neurotransmitters are generally stored in synaptic vesicles , clustered close to the cell membrane at the axon terminal of the presynaptic neuron. However, some neurotransmitters, like
2983-404: A neuron may release more than one transmitter from its synaptic terminal . Various techniques and experiments such as staining , stimulating, and collecting can be used to identify neurotransmitters throughout the central nervous system . Neurons communicate with each other through synapses , specialized contact points where neurotransmitters transmit signals. When an action potential reaches
3140-436: A neurotransmitter within the brain. Estrogen can be released by the ovary and function as a hormone or act locally via paracrine or autocrine signaling. Although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set of receptors and pathways. In fact, different organs in the body - even between different species - are known to utilize
3297-489: A pipe made from a small glass tube, often taken from " love roses ", small glass tubes with a paper rose that are promoted as romantic gifts. These are sometimes called "stems", "horns", "blasters" and "straight shooters". A small piece of clean heavy copper or occasionally stainless steel scouring pad – often called a "brillo" (actual Brillo Pads contain soap, and are not used) or "chore" (named for Chore Boy brand copper scouring pads) – serves as
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#17330863237163454-463: A receptor agonist is morphine , an opiate that mimics effects of the endogenous neurotransmitter β-endorphin to relieve pain. Other drugs interfere with the deactivation of a neurotransmitter after it has been released, thereby prolonging the action of a neurotransmitter. This can be accomplished by blocking re-uptake or inhibiting degradative enzymes. Lastly, drugs can also prevent an action potential from occurring, blocking neuronal activity throughout
3611-438: A reduction base and flow modulator in which the "rock" can be melted and boiled to vapor. Crack is smoked by placing it at the end of the pipe; a flame held close to it produces vapor, which is then inhaled by the smoker. The effects felt almost immediately after smoking, are very intense and do not last long — usually 2 to 10 minutes. When smoked, cocaine is sometimes combined with other drugs, such as cannabis , often rolled into
3768-418: A signal is one of the benefits to this multiple step sequence. Other benefits include more opportunities for regulation than simpler systems do and the fine-tuning of the response, in both unicellular and multicellular organism. In some cases, receptor activation caused by ligand binding to a receptor is directly coupled to the cell's response to the ligand. For example, the neurotransmitter GABA can activate
3925-521: A similar sets of paracrine factors in differential development. The highly conserved receptors and pathways can be organized into four major families based on similar structures: fibroblast growth factor (FGF) family, Hedgehog family, Wnt family, and TGF-β superfamily . Binding of a paracrine factor to its respective receptor initiates signal transduction cascades, eliciting different responses. Endocrine signals are called hormones . Hormones are produced by endocrine cells and they travel through
4082-426: A single step or as a series of changes in a sequence of different molecules (called a signal transduction pathway). The molecules that compose these pathways are known as relay molecules. The multistep process of the transduction stage is often composed of the activation of proteins by addition or removal of phosphate groups or even the release of other small molecules or ions that can act as messengers. The amplifying of
4239-486: A specific receptor . These molecules, also referred as ligands, are chemically diverse, including ions (e.g. Na+, K+, Ca++, etc.), lipids (e.g. steroid, prostaglandin), peptides (e.g. insulin, ACTH), carbohydrates, glycosylated proteins (proteoglycans), nucleic acids, etc. Peptide and lipid ligands are particularly important, as most hormones belong to these classes of chemicals. Peptides are usually polar, hydrophilic molecules. As such they are unable to diffuse freely across
4396-534: A spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes , including yeast , choanoflagellates , and animals. The ligands that bind and activate these receptors include light-sensitive compounds, odors , pheromones , hormones , and neurotransmitters , and vary in size from small molecules to peptides to large proteins . G protein-coupled receptors are involved in many diseases. There are two principal signal transduction pathways involving
4553-437: A stroke, irreversible brain damage, or a heart attack. Persons with regular or problematic use of cocaine have a significantly higher rate of death, and are specifically at higher risk of traumatic deaths and deaths attributable to infectious disease. The extent of absorption of cocaine into the systemic circulation after nasal insufflation is similar to that after oral ingestion. The rate of absorption after nasal insufflation
4710-491: A target cell as a ligand to cell surface receptors , and/or by entering into the cell through its membrane or endocytosis for intracrine signaling. This generally results in the activation of second messengers , leading to various physiological effects. In many mammals, early embryo cells exchange signals with cells of the uterus . In the human gastrointestinal tract , bacteria exchange signals with each other and with human epithelial and immune system cells. For
4867-405: A time period of hours to days. The best studied steroid hormone receptors are members of the nuclear receptor subfamily 3 (NR3) that include receptors for estrogen (group NR3A) and 3-ketosteroids (group NR3C). In addition to nuclear receptors, several G protein-coupled receptors and ion channels act as cell surface receptors for certain steroid hormones. Receptor mediated endocytosis
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5024-411: A topical anesthetic (eye drops) Prevents destruction of dopamine Signaling molecule Typically, the signaling process involves three components: the signal, the receptor, and the effector. In biology, signals are mostly chemical in nature, but can also be physical cues such as pressure , voltage , temperature , or light. Chemical signals are molecules with the ability to bind and activate
5181-418: Is a central nervous system stimulant. Its effects can last from 15 minutes to an hour. The duration of cocaine's effects depends on the amount taken and the route of administration. Cocaine can be in the form of fine white powder and has a bitter taste. Crack cocaine is a smokeable form of cocaine made into small "rocks" by processing cocaine with sodium bicarbonate (baking soda) and water. Crack cocaine
5338-413: Is a tropane alkaloid that acts as a central nervous system (CNS) stimulant . As an extract, it is mainly used recreationally and often illegally for its euphoric and rewarding effects. It is also used in medicine by Indigenous South Americans for various purposes and rarely, but more formally, as a local anaesthetic or diagnostic tool by medical practitioners in more developed countries. It
5495-732: Is a special case of paracrine signaling where the secreting cell has the ability to respond to the secreted signaling molecule. Synaptic signaling is a special case of paracrine signaling (for chemical synapses ) or juxtacrine signaling (for electrical synapses ) between neurons and target cells. Many cell signals are carried by molecules that are released by one cell and move to make contact with another cell. Signaling molecules can belong to several chemical classes: lipids , phospholipids , amino acids , monoamines , proteins , glycoproteins , or gases . Signaling molecules binding surface receptors are generally large and hydrophilic (e.g. TRH , Vasopressin , Acetylcholine ), while those entering
5652-412: Is also systemic, relating to disputes between crack dealers and users. Acute exposure may induce cardiac arrhythmias, including atrial fibrillation , supraventricular tachycardia , ventricular tachycardia , and ventricular fibrillation . Acute exposure may also lead to angina , heart attack , and congestive heart failure . Cocaine overdose may cause seizures , abnormally high body temperature and
5809-501: Is another dynamically developing field of pharmaceutical research. Enzyme-linked receptors (or catalytic receptors) are transmembrane receptors that, upon activation by an extracellular ligand , causes enzymatic activity on the intracellular side. Hence a catalytic receptor is an integral membrane protein possessing both enzymatic , catalytic , and receptor functions. They have two important domains, an extra-cellular ligand binding domain and an intracellular domain, which has
5966-517: Is associated with cancer, heart disease, and asthma. These trans-membrane receptors are able to transmit information from outside the cell to the inside because they change conformation when a specific ligand binds to it. There are three major types: Ion channel linked receptors , G protein–coupled receptors , and enzyme-linked receptors . Ion channel linked receptors are a group of transmembrane ion-channel proteins which open to allow ions such as Na , K , Ca , and/or Cl to pass through
6123-400: Is colloquially referred to as a "bell ringer". In a study of cocaine users, the average time taken to reach peak subjective effects was 3.1 minutes. The euphoria passes quickly. Aside from the toxic effects of cocaine, there is also the danger of circulatory emboli from the insoluble substances that may be used to cut the drug. As with all injected illicit substances , there is a risk of
6280-443: Is common way of turning receptors "off". Endocytic down regulation is regarded as a means for reducing receptor signaling. The process involves the binding of a ligand to the receptor, which then triggers the formation of coated pits, the coated pits transform to coated vesicles and are transported to the endosome. Receptor Phosphorylation is another type of receptor down-regulation. Biochemical changes can reduce receptor affinity for
6437-509: Is estimated to be 180 billion US dollars as of 2018 . It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia,
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6594-479: Is in a Type II, and the Type I synaptic cleft is wider. Finally, the active zone on a Type I synapse is larger than that on a Type II synapse. The different locations of Type I and Type II synapses divide a neuron into two zones: an excitatory dendritic tree and an inhibitory cell body. From an inhibitory perspective, excitation comes in over the dendrites and spreads to the axon hillock to trigger an action potential . If
6751-470: Is limited by cocaine-induced vasoconstriction of capillaries in the nasal mucosa. Onset of absorption after oral ingestion is delayed because cocaine is a weak base with a pKa of 8.6, and is thus in an ionized form that is poorly absorbed from the acidic stomach and easily absorbed from the alkaline duodenum. The rate and extent of absorption from inhalation of cocaine is similar or greater than with intravenous injection, as inhalation provides access directly to
6908-425: Is not what is involved in the habituation of the substance so much as the conformation and binding properties to where and how on the transporter the molecule binds. Conflicting findings have challenged the widely accepted view that cocaine functions solely as a reuptake inhibitor. To induce euphoria an intravenous dose of 0.3-0.6 mg/kg of cocaine is required, which blocks 66-70% of dopamine transporters (DAT) in
7065-406: Is occasionally used during surgery on the throat or inside of the nose to control pain, bleeding, and vocal cord spasm . Cocaine crosses the blood–brain barrier via a proton-coupled organic cation antiporter and (to a lesser extent) via passive diffusion across cell membranes . Cocaine blocks the dopamine transporter , inhibiting reuptake of dopamine from the synaptic cleft into
7222-417: Is possible in regular users until after the sections of hair grown during the period of cocaine use are cut or fall out. The pharmacodynamics of cocaine involve the complex relationships of neurotransmitters (inhibiting monoamine uptake in rats with ratios of about: serotonin :dopamine = 2:3, serotonin: norepinephrine = 2:5). The most extensively studied effect of cocaine on the central nervous system
7379-505: Is primarily obtained from the leaves of two Coca species native to South America: Erythroxylum coca and E. novogranatense . After extraction from the plant, and further processing into cocaine hydrochloride (powdered cocaine), the drug is administered by being either snorted , applied topically to the mouth , or dissolved and injected into a vein . It can also then be turned into free base form (typically crack cocaine ), in which it can be heated until sublimated and then
7536-434: Is programmed to respond to specific extracellular signal molecules, and is the basis of development , tissue repair , immunity , and homeostasis . Errors in signaling interactions may cause diseases such as cancer , autoimmunity , and diabetes . In many small organisms such as bacteria , quorum sensing enables individuals to begin an activity only when the population is sufficiently large. This signaling between cells
7693-521: Is referred to as "crack" because of the crackling sounds it makes when heated. Cocaine use leads to increases in alertness, feelings of well-being and euphoria , increased energy and motor activity, and increased feelings of competence and sexuality. Analysis of the correlation between the use of 18 various psychoactive substances shows that cocaine use correlates with other " party drugs " (such as ecstasy or amphetamines ), as well as with heroin and benzodiazepines use, and can be considered as
7850-447: Is responsible for the interaction with a specific ligand. The intracellular domain is responsible for the initiation of a cascade of chemical reactions which ultimately triggers the specific cellular function controlled by the receptor. Enzyme-linked receptors are transmembrane proteins with an extracellular domain responsible for binding a specific ligand and an intracellular domain with enzymatic or catalytic activity. Upon activation
8007-434: Is that the smoking of cocaine chemically breaks down tooth enamel and causes tooth decay . Cocaine can cause involuntary tooth grinding, known as bruxism , which can deteriorate tooth enamel and lead to gingivitis . Additionally, stimulants like cocaine, methamphetamine, and even caffeine cause dehydration and dry mouth . Since saliva is an important mechanism in maintaining one's oral pH level, people who use cocaine over
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#17330863237168164-470: Is the MAPK/ERK pathway, which involves changes of protein–protein interactions inside the cell, induced by an external signal. Many growth factors bind to receptors at the cell surface and stimulate cells to progress through the cell cycle and divide . Several of these receptors are kinases that start to phosphorylate themselves and other proteins when binding to a ligand. This phosphorylation can generate
8321-404: Is the blockade of the dopamine transporter protein. Dopamine neurotransmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the presynaptic neuron , where it is taken up into storage vesicles . Cocaine binds tightly at the dopamine transporter forming a complex that blocks
8478-424: Is the result of the transduced signal in the final stage of cell signaling. This response can essentially be any cellular activity that is present in a body. It can spur the rearrangement of the cytoskeleton, or even as catalysis by an enzyme. These three steps of cell signaling all ensure that the right cells are behaving as told, at the right time, and in synchronization with other cells and their own functions within
8635-406: The 5-HT 3 receptor , which is a ligand-gated ion channel . An overabundance of 5-HT 3 receptors is reported in cocaine-conditioned rats, though 5-HT 3 's role is unclear. The 5-HT 2 receptor (particularly the subtypes 5-HT 2A , 5-HT 2B and 5-HT 2C ) are involved in the locomotor-activating effects of cocaine. Cocaine has been demonstrated to bind as to directly stabilize
8792-445: The DAT transporter on the open outward-facing conformation. Further, cocaine binds in such a way as to inhibit a hydrogen bond innate to DAT. Cocaine's binding properties are such that it attaches so this hydrogen bond will not form and is blocked from formation due to the tightly locked orientation of the cocaine molecule. Research studies have suggested that the affinity for the transporter
8949-631: The Single Convention on Narcotic Drugs has required countries to make recreational use of cocaine a crime . In the United States, cocaine is regulated as a Schedule II drug under the Controlled Substances Act , meaning that it has a high potential for abuse but has an accepted medical use. While rarely used medically today, its accepted uses are as a topical local anesthetic for the upper respiratory tract as well as to reduce bleeding in
9106-415: The blood to reach all parts of the body. Specificity of signaling can be controlled if only some cells can respond to a particular hormone. Endocrine signaling involves the release of hormones by internal glands of an organism directly into the circulatory system , regulating distant target organs. In vertebrates , the hypothalamus is the neural control center for all endocrine systems. In humans ,
9263-534: The cartilage separating the nostrils (the septum nasi ), leading eventually to its complete disappearance. Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid. Illicitly-sold cocaine may be contaminated with levamisole. Levamisole may accentuate cocaine's effects. Levamisole-adulterated cocaine has been associated with autoimmune disease. Cocaine use leads to an increased risk of hemorrhagic and ischemic strokes . Cocaine use also increases
9420-407: The cell membrane seven times. The G-protein acts as a "middle man" transferring the signal from its activated receptor to its target and therefore indirectly regulates that target protein. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although
9577-576: The central nervous system . Single ions (such as synaptically released zinc ) are also considered neurotransmitters by some, as well as some gaseous molecules such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H 2 S). The gases are produced in the neural cytoplasm and are immediately diffused through the cell membrane into the extracellular fluid and into nearby cells to stimulate production of second messengers. Soluble gas neurotransmitters are difficult to study, as they act rapidly and are immediately broken down, existing for only
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#17330863237169734-423: The circulatory system ; juxtacrine interactions ; and autocrine signaling . Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain. Paracrine signals such as retinoic acid target only cells in
9891-453: The hydrophobic portion of the cell membrane by passive transport . Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes . Porosomes are permanent cup-shaped lipoprotein structures at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from
10048-543: The immune response . Juxtacrine signalling via direct membrane contacts is also present between neuronal cell bodies and motile processes of microglia both during development, and in the adult brain. In paracrine signaling, a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance (local action), as opposed to cell signaling by endocrine factors , hormones which travel considerably longer distances via
10205-604: The liver to form cocaethylene . Studies have suggested cocaethylene is more euphoric , and has a higher cardiovascular toxicity than cocaine by itself. Depending on liver and kidney functions, cocaine metabolites are detectable in urine between three and eight days. Generally speaking benzoylecgonine is eliminated from someone's urine between three and five days. In urine from heavy cocaine users, benzoylecgonine can be detected within four hours after intake and in concentrations greater than 150 ng/mL for up to eight days later. Detection of cocaine metabolites in hair
10362-484: The membrane potential . LICs are classified into three superfamilies which lack evolutionary relationship: cys-loop receptors , ionotropic glutamate receptors and ATP-gated channels . G protein-coupled receptors are a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. Coupling with G proteins , they are called seven-transmembrane receptors because they pass through
10519-547: The mouth against the inner cheek ; it has traditionally been used to combat the effects of cold, hunger, and altitude sickness . Cocaine was first isolated from the leaves in 1860. Globally, in 2019, cocaine was used by an estimated 20 million people (0.4% of adults aged 15 to 64 years). The highest prevalence of cocaine use was in Australia and New Zealand (2.1%), followed by North America (2.1%), Western and Central Europe (1.4%), and South and Central America (1.0%). Since 1961,
10676-422: The presynaptic terminal , the action potential can trigger the release of neurotransmitters into the synaptic cleft. These neurotransmitters then bind to receptors on the postsynaptic membrane, influencing the receiving neuron in either an inhibitory or excitatory manner. If the overall excitatory influences outweigh the inhibitory influences, the receiving neuron may generate its own action potential, continuing
10833-488: The synaptic cleft via exocytosis; however, neurotransmitters can also be released via reverse transport through membrane transport proteins . Autocrine signaling involves a cell secreting a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell itself. This can be contrasted with paracrine signaling , intracrine signaling, or classical endocrine signaling. In intracrine signaling,
10990-438: The synaptic cleft , was discovered. The presence of such a gap suggested communication via chemical messengers traversing the synaptic cleft, and in 1921 German pharmacologist Otto Loewi confirmed that neurons can communicate by releasing chemicals. Through a series of experiments involving the vagus nerves of frogs, Loewi was able to manually slow the heart rate of frogs by controlling the amount of saline solution present around
11147-495: The synaptic cleft , where they bind to specific receptors on the membrane of the postsynaptic neuron. After being released into the synaptic cleft, neurotransmitters diffuse across the synapse where they are able to interact with receptors on the target cell. The effect of the neurotransmitter is dependent on the identity of the target cell's receptors present at the synapse. Depending on the receptor, binding of neurotransmitters may cause excitation , inhibition , or modulation of
11304-616: The Andes to prevent altitude sickness . Its actual effectiveness has never been systematically studied. In 1986 an article in the Journal of the American Medical Association revealed that U.S. health food stores were selling dried coca leaves to be prepared as an infusion as "Health Inca Tea". While the packaging claimed it had been "decocainized", no such process had actually taken place. The article stated that drinking two cups of
11461-443: The D 1 dopamine receptor. Cocaine also blocks sodium channels , thereby interfering with the propagation of action potentials ; thus, like lignocaine and novocaine , it acts as a local anesthetic. It also functions on the binding sites to the dopamine and serotonin sodium dependent transport area as targets as separate mechanisms from its reuptake of those transporters; unique to its local anesthetic value which makes it in
11618-495: The G protein-coupled receptors: cAMP signal pathway and phosphatidylinositol signal pathway. When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP . The G protein's α subunit, together with
11775-547: The Global Burden of Disease study found that cocaine use caused around 7,300 deaths annually. Coca leaves have been used by Andean civilizations since ancient times . In ancient Wari culture , Inca culture, and through modern successor indigenous cultures of the Andes mountains , coca leaves are chewed, taken orally in the form of a tea , or alternatively, prepared in a sachet wrapped around alkaline burnt ashes, and held in
11932-638: The United States in December 2017, and is indicated for the introduction of local anesthesia of the mucous membranes for diagnostic procedures and surgeries on or through the nasal cavities of adults. Cocaine hydrochloride ( Numbrino ) was approved for medical use in the United States in January 2020. The most common adverse reactions in people treated with Goprelto are headache and epistaxis . The most common adverse reactions in people treated with Numbrino are hypertension, tachycardia, and sinus tachycardia. Cocaine
12089-419: The United States warned about health risks while cautioning against stereotyping: Many recall that "crack babies", or babies born to mothers who used crack cocaine while pregnant, were at one time written off by many as a lost generation. They were predicted to suffer from severe, irreversible damage, including reduced intelligence and social skills. It was later found that this was a gross exaggeration. However,
12246-455: The acetylation or methylation of histones at the sites of repair. These alterations can be epigenetic scars in the chromatin that contribute to the persistent epigenetic changes found in cocaine addiction . In humans, cocaine abuse may cause structural changes in brain connectivity, though it is unclear to what extent these changes are permanent. Cocaine dependence develops after even brief periods of regular cocaine use and produces
12403-466: The actions of some neurotransmitter systems, often acting through transmitters other than glutamate or GABA. Addictive drugs such as cocaine and amphetamines exert their effects primarily on the dopamine system. The addictive opiate drugs exert their effects primarily as functional analogs of opioid peptides , which, in turn, regulate dopamine levels. Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of
12560-674: The baby to grow poorly. As a result, cocaine-exposed babies are more likely than unexposed babies to be born with low birth weight (less than 5.5 lb or 2.5 kg). Low-birthweight babies are 20 times more likely to die in their first month of life than normal-weight babies, and face an increased risk of lifelong disabilities such as mental retardation and cerebral palsy. Cocaine-exposed babies also tend to have smaller heads, which generally reflect smaller brains. Some studies suggest that cocaine-exposed babies are at increased risk of birth defects, including urinary tract defects and, possibly, heart defects. Cocaine also may cause an unborn baby to have
12717-456: The bi-lipid layer of the plasma membrane, so their action is mediated by a cell membrane bound receptor. On the other hand, liposoluble chemicals such as steroid hormones, can diffuse passively across the plasma membrane and interact with intracellular receptors. Cell signaling can occur over short or long distances, and can be further classified as autocrine , intracrine , juxtacrine , paracrine , or endocrine . Autocrine signaling occurs when
12874-400: The blood. Receptors are complex proteins or tightly bound multimer of proteins, located in the plasma membrane or within the interior of the cell such as in the cytoplasm , organelles , and nucleus . Receptors have the ability to detect a signal either by binding to a specific chemical or by undergoing a conformational change when interacting with physical agents. It is the specificity of
13031-492: The body. They then reach target cells, which can recognize and respond to the hormones and produce a result. This is also known as endocrine signaling. Plant growth regulators, or plant hormones, move through cells or by diffusing through the air as a gas to reach their targets. Hydrogen sulfide is produced in small amounts by some cells of the human body and has a number of biological signaling functions. Only two other such gases are currently known to act as signaling molecules in
13188-454: The bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type ( G αs , G αi/o , G αq/11 , G α12/13 ). G protein-coupled receptors are an important drug target and approximately 34% of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs
13345-625: The brain via signaling through trace amine-associated receptor 1 . A brief comparison of these systems follows: Caudal nuclei (CN): Raphe magnus , raphe pallidus , and raphe obscurus Rostral nuclei (RN): Nucleus linearis , dorsal raphe , medial raphe , and raphe pontis Forebrain cholinergic nuclei (FCN): Nucleus basalis of Meynert , medial septal nucleus , and diagonal band Striatal tonically active cholinergic neurons (TAN) Brainstem cholinergic nuclei (BCN): Pedunculopontine nucleus , laterodorsal tegmentum , medial habenula , and parabigeminal nucleus Understanding
13502-449: The brain. Re-administering cocaine beyond this threshold does not significantly increase DAT occupancy but still results in an increase of euphoria which cannot be explained by reuptake inhibition alone. This discrepancy is not shared with other dopamine reuptake inhbitors like bupropion , sibutramine , mazindol or tesofensine , which have similar or higher potencies than cocaine as dopamine reuptake inhibitors. These findings have evoked
13659-625: The breakdown of the blood–brain barrier. Physical side effects from chronic smoking of cocaine include coughing up blood , bronchospasm , itching , fever , diffuse alveolar infiltrates without effusions, pulmonary and systemic eosinophilia , chest pain, lung trauma, sore throat, asthma , hoarse voice, dyspnea (shortness of breath), and an aching, flu -like syndrome. Cocaine constricts blood vessels , dilates pupils , and increases body temperature, heart rate, and blood pressure. It can also cause headaches and gastrointestinal complications such as abdominal pain and nausea. A common but untrue belief
13816-403: The cell are generally small and hydrophobic (e.g. glucocorticoids , thyroid hormones , cholecalciferol , retinoic acid ), but important exceptions to both are numerous, and the same molecule can act both via surface receptors or in an intracrine manner to different effects. In animal cells, specialized cells release these hormones and send them through the circulatory system to other parts of
13973-466: The cell's response. The activated receptor must first interact with other proteins inside the cell before the ultimate physiological effect of the ligand on the cell's behavior is produced. Often, the behavior of a chain of several interacting cell proteins is altered following receptor activation. The entire set of cell changes induced by receptor activation is called a signal transduction mechanism or pathway. A more complex signal transduction pathway
14130-442: The cell. In exocytosis, membrane-bound secretory vesicles are carried to the cell membrane , where they dock and fuse at porosomes and their contents (i.e., water-soluble molecules) are secreted into the extracellular environment. This secretion is possible because the vesicle transiently fuses with the plasma membrane. In the context of neurotransmission , neurotransmitters are typically released from synaptic vesicles into
14287-404: The cell. Classes of neurotransmitters include amino acids , monoamines , and peptides . Monoamines are synthesized by altering a single amino acid. For example, the precursor of serotonin is the amino acid tryptophan. Peptide neurotransmitters, or neuropeptides , are protein transmitters which are larger than the classical small-molecule neurotransmitters and are often released together to elicit
14444-455: The central and peripheral nervous system . Drugs such as tetrodotoxin that block neural activity are typically lethal. Drugs targeting the neurotransmitter of major systems affect the whole system, which can explain the complexity of action of some drugs. Cocaine , for example, blocks the re-uptake of dopamine back into the presynaptic neuron, leaving the neurotransmitter molecules in the synaptic gap for an extended period of time. Since
14601-433: The chemical interaction between a given ligand and its receptor that confers the ability to trigger a specific cellular response. Receptors can be broadly classified into cell membrane receptors and intracellular receptors. Cell membrane receptors can be further classified into ion channel linked receptors, G-Protein coupled receptors and enzyme linked receptors. Ion channels receptors are large transmembrane proteins with
14758-434: The chemical signal acts on the same cell that produced the signaling chemical. Intracrine signaling occurs when the chemical signal produced by a cell acts on receptors located in the cytoplasm or nucleus of the same cell. Juxtacrine signaling occurs between physically adjacent cells. Paracrine signaling occurs between nearby cells. Endocrine interaction occurs between distant cells, with the chemical signal usually carried by
14915-450: The dopamine remains in the synapse longer, the neurotransmitter continues to bind to the receptors on the postsynaptic neuron, eliciting a pleasurable emotional response. Physical addiction to cocaine may result from prolonged exposure to excess dopamine in the synapses, which leads to the downregulation of some post-synaptic receptors. After the effects of the drug wear off, an individual can become depressed due to decreased probability of
15072-519: The effects of drugs on neurotransmitters comprises a significant portion of research initiatives in the field of neuroscience . Most neuroscientists involved in this field of research believe that such efforts may further advance our understanding of the circuits responsible for various neurological diseases and disorders, as well as ways to effectively treat and someday possibly prevent or cure such illnesses. Drugs can influence behavior by altering neurotransmitter activity. For instance, drugs can decrease
15229-438: The enzymatic portion is responsible for promoting specific intracellular chemical reactions. Intracellular receptors have a different mechanism of action. They usually bind to lipid soluble ligands that diffuse passively through the plasma membrane such as steroid hormones. These ligands bind to specific cytoplasmic transporters that shuttle the hormone-transporter complex inside the nucleus where specific genes are activated and
15386-764: The euphoric effects of cocaine begins after about one hour. With excessive or prolonged use, the drug can cause itching , fast heart rate , and paranoid delusions or sensations of insects crawling on the skin . Intranasal cocaine and crack use are both associated with pharmacological violence. Aggressive behavior may be displayed by both addicts and casual users. Cocaine can induce psychosis characterized by paranoia, impaired reality testing , hallucinations , irritability, and physical aggression. Cocaine intoxication can cause hyperawareness, hypervigilance , and psychomotor agitation and delirium . Consumption of large doses of cocaine can cause violent outbursts, especially by those with preexisting psychosis. Crack-related violence
15543-512: The eye to sublimated cocaine while smoking crack cocaine can cause serious injury to the cornea and long-term loss of visual acuity. Although it has been commonly asserted, the available evidence does not show that chronic use of cocaine is associated with broad cognitive deficits. Research is inconclusive on age-related loss of striatal dopamine transporter (DAT) sites, suggesting cocaine has neuroprotective or neurodegenerative properties for dopamine neurons. Exposure to cocaine may lead to
15700-504: The fact that most of these children appear normal should not be over-interpreted as indicating that there is no cause for concern. Using sophisticated technologies, scientists are now finding that exposure to cocaine during fetal development may lead to subtle, yet significant, later deficits in some children, including deficits in some aspects of cognitive performance, information-processing, and attention to tasks—abilities that are important for success in school. There are also warnings about
15857-557: The gates" strategy, the excitatory message is like a racehorse ready to run down the track, but first, the inhibitory starting gate must be removed. As explained above, the only direct action of a neurotransmitter is to activate a receptor. Therefore, the effects of a neurotransmitter system depend on the connections of the neurons that use the transmitter, and the chemical properties of the receptors. There are many different ways to classify neurotransmitters and are commonly classified into amino acids , monoamines and peptides . Some of
16014-555: The growth factor receptors (such as EGFR) that initiate this signal transduction pathway. Some signaling transduction pathways respond differently, depending on the amount of signaling received by the cell. For instance, the hedgehog protein activates different genes, depending on the amount of hedgehog protein present. Complex multi-component signal transduction pathways provide opportunities for feedback, signal amplification, and interactions inside one cell between multiple signals and signaling pathways. A specific cellular response
16171-505: The human body: nitric oxide and carbon monoxide . Exocytosis is the process by which a cell transports molecules such as neurotransmitters and proteins out of the cell. As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis , the process that brings substances into the cell, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through
16328-593: The influence of a chemical signal, known as an acrasin . The individuals move by chemotaxis , i.e. they are attracted by the chemical gradient. Some species use cyclic AMP as the signal; others such as Polysphondylium violaceum use a dipeptide known as glorin . In plants and animals, signaling between cells occurs either through release into the extracellular space , divided in paracrine signaling (over short distances) and endocrine signaling (over long distances), or by direct contact, known as juxtacrine signaling such as notch signaling . Autocrine signaling
16485-673: The initiation of a second messenger system cascade that propagates the signal through the cell. Second messenger systems can amplify or modulate a signal, in which activation of a few receptors results in multiple secondary messengers being activated, thereby amplifying the initial signal (the first messenger). The downstream effects of these signaling pathways may include additional enzymatic activities such as proteolytic cleavage , phosphorylation , methylation , and ubiquitinylation . Signaling molecules can be synthesized from various biosynthetic pathways and released through passive or active transports , or even from cell damage . Each cell
16642-484: The ion channels, which leads to a flow of ions across the cell membrane. This, in turn, results in either a depolarization , for an excitatory receptor response, or a hyperpolarization , for an inhibitory response. These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain which includes the ligand binding location (an allosteric binding site). This modularity has enabled
16799-417: The major endocrine glands are the thyroid gland and the adrenal glands . The study of the endocrine system and its disorders is known as endocrinology . Cells receive information from their neighbors through a class of proteins known as receptors . Receptors may bind with some molecules (ligands) or may interact with physical agents like light, mechanical temperature, pressure, etc. Reception occurs when
16956-446: The major neurotransmitters are: In addition, over 100 neuroactive peptides have been found, and new ones are discovered regularly. Many of these are co-released along with a small-molecule transmitter. Nevertheless, in some cases, a peptide is the primary transmitter at a synapse. Beta-Endorphin is a relatively well-known example of a peptide neurotransmitter because it engages in highly specific interactions with opioid receptors in
17113-436: The mechanisms of cocaine addiction. The onset of cocaine's euphoric effects is fastest with inhalation, beginning after 3–5 seconds. This gives the briefest euphoria (5–15 minutes). Cocaine is smoked by inhaling the vapor produced when crack cocaine is heated to the point of sublimation. In a 2000 Brookhaven National Laboratory medical department study, based on self-reports of 32 people who used cocaine who participated in
17270-404: The membrane in response to the binding of a chemical messenger (i.e. a ligand ), such as a neurotransmitter . When a presynaptic neuron is excited, it releases a neurotransmitter from vesicles into the synaptic cleft . The neurotransmitter then binds to receptors located on the postsynaptic neuron . If these receptors are ligand-gated ion channels, a resulting conformational change opens
17427-437: The message is to be stopped, it is best stopped by applying inhibition on the cell body, close to the axon hillock where the action potential originates. Another way to conceptualize excitatory–inhibitory interaction is to picture excitation overcoming inhibition. If the cell body is normally in an inhibited state, the only way to generate an action potential at the axon hillock is to reduce the cell body's inhibition. In this "open
17584-481: The metabolic gases carbon monoxide and nitric oxide, are synthesized and released immediately following an action potential without ever being stored in vesicles. Generally, a neurotransmitter is released via exocytosis at the presynaptic terminal in response to an electrical signal called an action potential in the presynaptic neuron. However, low-level "baseline" release also occurs without electrical stimulation. Neurotransmitters are released into and diffuse across
17741-399: The mouth, throat and nasal cavities. Cocaine eye drops are frequently used by neurologists when examining patients suspected of having Horner syndrome . In Horner syndrome, sympathetic innervation to the eye is blocked. In a healthy eye, cocaine will stimulate the sympathetic nerves by inhibiting norepinephrine reuptake, and the pupil will dilate; if the patient has Horner syndrome,
17898-437: The neurons under its influence. Receptors with modulatory effects are spread throughout all synaptic membranes and binding of neurotransmitters sets in motion signaling cascades that help the cell regulate its function. Binding of neurotransmitters to receptors with modulatory effects can have many results. For example, it may result in an increase or decrease in sensitivity to future stimulus by recruiting more or less receptors to
18055-408: The neurotransmitter binding to a receptor. Fluoxetine is a selective serotonin re-uptake inhibitor (SSRI), which blocks re-uptake of serotonin by the presynaptic cell which increases the amount of serotonin present at the synapse and furthermore allows it to remain there longer, providing potential for the effect of naturally released serotonin. AMPT prevents the conversion of tyrosine to L-DOPA ,
18212-414: The nose by about five minutes. This occurs because cocaine's absorption is slowed by its constricting effect on the blood vessels of the nose. Insufflation of cocaine also leads to the longest duration of its effects (60–90 minutes). When insufflating cocaine, absorption through the nasal membranes is approximately 30–60% In a study of cocaine users, the average time taken to reach peak subjective effects
18369-492: The number of dendritic branches and spines present on neurons involved with the nucleus accumbens and prefrontal cortex areas of the brain. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug. Transgenic mice exhibiting inducible expression of ΔFosB primarily in the nucleus accumbens and dorsal striatum exhibit sensitized behavioural responses to cocaine. They self-administer cocaine at lower doses than control, but have
18526-433: The organism. At the end, the end of a signal pathway leads to the regulation of a cellular activity. This response can take place in the nucleus or in the cytoplasm of the cell. A majority of signaling pathways control protein synthesis by turning certain genes on and off in the nucleus. Cocaine Cocaine (from French cocaïne , from Spanish coca , ultimately from Quechua kúka )
18683-499: The overall risk of death, and intravenous use potentially increases the risk of trauma and infectious diseases such as blood infections and HIV through the use of shared paraphernalia . It also increases risk of stroke , heart attack , cardiac arrhythmia, lung injury (when smoked), and sudden cardiac death . Illicitly sold cocaine can be adulterated with fentanyl , local anesthetics , levamisole , cornstarch, quinine , or sugar, which can result in additional toxicity. In 2017,
18840-516: The peak effects are attained. Cocaine crosses the blood–brain barrier via both a proton-coupled organic cation antiporter and (to a lesser extent) via passive diffusion across cell membranes . As of September 2022, the gene or genes encoding the human proton-organic cation antiporter had not been identified. Cocaine has a short elimination half life of 0.7–1.5 hours and is extensively metabolized by plasma esterases and also by liver cholinesterases , with only about 1% excreted unchanged in
18997-584: The post-synaptic neuron, contributing to the mental and physical effects of cocaine exposure. A single dose of cocaine induces tolerance to the drug's effects. Repeated use is likely to result in addiction . Addicts who abstain from cocaine may experience prolonged craving lasting for many months. Abstaining addicts also experience modest drug withdrawal symptoms lasting up to 24 hours, with sleep disruption, anxiety, irritability, crashing, depression , decreased libido , decreased ability to feel pleasure , and fatigue being common. Use of cocaine increases
19154-414: The postsynaptic neuron. In order to avoid continuous activation of receptors on the post-synaptic or target cell, neurotransmitters must be removed from the synaptic cleft. Neurotransmitters are removed through one of three mechanisms: For example, acetylcholine is eliminated by having its acetyl group cleaved by the enzyme acetylcholinesterase ; the remaining choline is then taken in and recycled by
19311-469: The pre-synaptic axon terminal ; the higher dopamine levels in the synaptic cleft increase dopamine receptor activation in the post-synaptic neuron, causing euphoria and arousal. Cocaine also blocks the serotonin transporter and norepinephrine transporter , inhibiting reuptake of serotonin and norepinephrine from the synaptic cleft into the pre-synaptic axon terminal and increasing activation of serotonin receptors and norepinephrine receptors in
19468-434: The pre-synaptic neuron to synthesize more acetylcholine . Other neurotransmitters are able to diffuse away from their targeted synaptic junctions and are eliminated from the body via the kidneys, or destroyed in the liver. Each neurotransmitter has very specific degradation pathways at regulatory points, which may be targeted by the body's regulatory system or medication. Cocaine blocks a dopamine transporter responsible for
19625-698: The precursor to dopamine; reserpine prevents dopamine storage within vesicles ; and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels. Prevents muscle contractions Stimulates muscle contractions Increases effects of ACh at receptors Used to treat myasthenia gravis Increases attention Reinforcing effects Prevents muscle contractions Toxic Blocks saliva production Causes sedation and depression High dose: stimulates postsynaptic receptors Blocks reuptake Blocks reuptake Enhances attention and impulse control in ADHD Blocks voltage-dependent sodium channels Can be used as
19782-410: The presence of nuclear and mitochondrial receptors is well documented. The binding of a ligand to the intracellular receptor typically induces a response in the cell. Intracellular receptors often have a level of specificity, this allows the receptors to initiate certain responses when bound to a corresponding ligand. Intracellular receptors typically act on lipid soluble molecules. The receptors bind to
19939-423: The probability that the cell with which it comes in contact will produce an action potential. Synapses containing receptors with excitatory effects are called Type I synapses, while Type II synapses contain receptors with inhibitory effects. Thus, despite the wide variety of synapses, they all convey messages of only these two types. The two types are different appearance and are primarily located on different parts of
20096-578: The pulmonary capillary bed. The delay in absorption after oral ingestion may account for the popular belief that cocaine bioavailability from the stomach is lower than after insufflation. Compared with ingestion, the faster absorption of insufflated cocaine results in quicker attainment of maximum drug effects. Snorting cocaine produces maximum physiological effects within 40 minutes and maximum psychotropic effects within 20 minutes. Physiological and psychotropic effects from nasally insufflated cocaine are sustained for approximately 40–60 minutes after
20253-452: The rate of synthesis of neurotransmitters by affecting the synthetic enzyme(s) for that neurotransmitter. When neurotransmitter syntheses are blocked, the amount of neurotransmitters available for release becomes substantially lower, resulting in a decrease in neurotransmitter activity. Some drugs block or stimulate the release of specific neurotransmitters. Alternatively, drugs can prevent neurotransmitter storage in synaptic vesicles by causing
20410-422: The reuptake of dopamine. Without the transporter, dopamine diffuses much more slowly from the synaptic cleft and continues to activate the dopamine receptors on the target cell. Until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through histological examinations by Ramón y Cajal , a 20 to 40 nm gap between neurons, known today as
20567-598: The risk of having a heart attack . Relatives of persons with cocaine addiction have an increased risk of cocaine addiction. Cocaine addiction occurs through ΔFosB overexpression in the nucleus accumbens , which results in altered transcriptional regulation in neurons within the nucleus accumbens . ΔFosB levels have been found to increase upon the use of cocaine. Each subsequent dose of cocaine continues to increase ΔFosB levels with no ceiling of tolerance. Elevated levels of ΔFosB leads to increases in brain-derived neurotrophic factor ( BDNF ) levels, which in turn increases
20724-401: The same as chewing tobacco is chewed) and sucked of its juices. The juices are absorbed slowly by the mucous membrane of the inner cheek and by the gastrointestinal tract when swallowed. Alternatively, coca leaves can be infused in liquid and consumed like tea. Coca tea , an infusion of coca leaves, is also a traditional method of consumption. The tea has often been recommended for travelers in
20881-489: The signal has an effect on the cell that produced it. Juxtacrine signaling is a type of cell –cell or cell– extracellular matrix signaling in multicellular organisms that requires close contact. There are three types: Additionally, in unicellular organisms such as bacteria , juxtacrine signaling means interactions by membrane contact. Juxtacrine signaling has been observed for some growth factors , cytokine and chemokine cellular signals, playing an important role in
21038-577: The signal transduction pathways that are activated is called the mitogen-activated protein kinase (MAPK) pathway. The signal transduction component labeled as "MAPK" in the pathway was originally called "ERK," so the pathway is called the MAPK/ERK pathway . The MAPK protein is an enzyme, a protein kinase that can attach phosphate to target proteins such as the transcription factor MYC and, thus, alter gene transcription and, ultimately, cell cycle progression. Many cellular proteins are activated downstream of
21195-433: The signaling chemicals are produced inside the cell and bind to cytosolic or nuclear receptors without being secreted from the cell.. In intracrine signaling, signals are relayed without being secreted from the cell. The intracrine signals not being secreted outside of the cell is what sets apart intracrine signaling from the other cell signaling mechanisms such as autocrine signaling. In both autocrine and intracrine signaling,
21352-451: The study, "peak high" was found at a mean of 1.4 ± 0.5 minutes. Pyrolysis products of cocaine that occur only when heated/smoked have been shown to change the effect profile, i.e. anhydroecgonine methyl ester , when co-administered with cocaine, increases the dopamine in CPu and NAc brain regions, and has M 1 — and M 3 — receptor affinity. People often freebase crack with
21509-491: The sympathetic nerves are blocked, and the affected eye will remain constricted or dilate to a lesser extent than the opposing (unaffected) eye which also receives the eye drop test. If both eyes dilate equally, the patient does not have Horner syndrome. Topical cocaine is sometimes used as a local numbing agent and vasoconstrictor to help control pain and bleeding with surgery of the nose, mouth, throat or lacrimal duct . Although some absorption and systemic effects may occur,
21666-406: The synaptic membrane. Type I (excitatory) synapses are typically located on the shafts or the spines of dendrites, whereas type II (inhibitory) synapses are typically located on a cell body. In addition, Type I synapses have round synaptic vesicles, whereas the vesicles of type II synapses are flattened. The material on the presynaptic and post-synaptic membranes is denser in a Type I synapse than it
21823-450: The synaptic vesicle membranes to leak. Drugs that prevent a neurotransmitter from binding to its receptor are called receptor antagonists . For example, drugs used to treat patients with schizophrenia such as haloperidol, chlorpromazine, and clozapine are antagonists at receptors in the brain for dopamine. Other drugs act by binding to a receptor and mimicking the normal neurotransmitter. Such drugs are called receptor agonists . An example of
21980-405: The synthesis of specific proteins is promoted. The effector component of the signaling pathway begins with signal transduction . In this process, the signal, by interacting with the receptor, starts a series of molecular events within the cell leading to the final effect of the signaling process. Typically the final effect consists in the activation of an ion channel ( ligand-gated ion channel ) or
22137-404: The system affects large volumes of the brain, called volume transmission . Major neurotransmitter systems include the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system, and the cholinergic system, among others. Trace amines have a modulatory effect on neurotransmission in monoamine pathways (i.e., dopamine, norepinephrine, and serotonin pathways) throughout
22294-428: The target cell (any cell with a receptor protein specific to the signal molecule ) detects a signal, usually in the form of a small, water-soluble molecule, via binding to a receptor protein on the cell surface, or once inside the cell, the signaling molecule can bind to intracellular receptors , other elements, or stimulate enzyme activity (e.g. gasses), as in intracrine signaling. Signaling molecules interact with
22451-700: The target cell is determined by the receptor it binds to. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids , which are readily available and often require a small number of biosynthetic steps for conversion. Neurotransmitters are essential to the function of complex neural systems. The exact number of unique neurotransmitters in humans is unknown, but more than 100 have been identified. Common neurotransmitters include glutamate , GABA , acetylcholine , glycine , dopamine and norepinephrine . Neurotransmitters are generally synthesized in neurons and are made up of, or derived from, precursor molecules that are found abundantly in
22608-437: The tea per day gave a mild stimulation , increased heart rate , and mood elevation, and the tea was essentially harmless. Nasal insufflation (known colloquially as "snorting", "sniffing", or "blowing") is a common method of ingestion of recreational powdered cocaine. The drug coats and is absorbed through the mucous membranes lining the nasal passages . Cocaine's desired euphoric effects are delayed when snorted through
22765-441: The term "neurotransmitter" can be applied to chemicals that: The anatomical localization of neurotransmitters is typically determined using immunocytochemical techniques, which identify the location of either the transmitter substances themselves or of the enzymes that are involved in their synthesis. Immunocytochemical techniques have also revealed that many transmitters, particularly the neuropeptides , are co-localized, that is,
22922-470: The threat of breastfeeding : The March of Dimes said "it is likely that cocaine will reach the baby through breast milk," and advises the following regarding cocaine use during pregnancy: Cocaine use during pregnancy can affect a pregnant woman and her unborn baby in many ways. During the early months of pregnancy, it may increase the risk of miscarriage. Later in pregnancy, it can trigger preterm labor (labor that occurs before 37 weeks of pregnancy) or cause
23079-478: The transmission of information to the next neuron in the network. This process allows for the flow of information and the formation of complex neural networks. A neurotransmitter may have an excitatory, inhibitory or modulatory effect on the target cell. The effect is determined by the receptors the neurotransmitter interacts with at the post-synaptic membrane. Neurotransmitter influences trans-membrane ion flow either to increase (excitatory) or to decrease (inhibitory)
23236-432: The transporter's function. The dopamine transporter can no longer perform its reuptake function, and thus dopamine accumulates in the synaptic cleft . The increased concentration of dopamine in the synapse activates post-synaptic dopamine receptors, which makes the drug rewarding and promotes the compulsive use of cocaine. Cocaine affects certain serotonin (5-HT) receptors; in particular, it has been shown to antagonize
23393-486: The urine. The metabolism is dominated by hydrolytic ester cleavage, so the eliminated metabolites consist mostly of benzoylecgonine (BE), the major metabolite , and other metabolites in lesser amounts such as ecgonine methyl ester (EME) and ecgonine . Further minor metabolites of cocaine include norcocaine , p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. If consumed with alcohol , cocaine combines with alcohol in
23550-408: The use of cocaine as a topical anesthetic and vasoconstrictor is generally safe, rarely causing cardiovascular toxicity, glaucoma , and pupil dilation . Occasionally, cocaine is mixed with adrenaline and sodium bicarbonate and used topically for surgery, a formulation called Moffett's solution . Cocaine hydrochloride ( Goprelto ), an ester local anesthetic, was approved for medical use in
23707-648: The user contracting blood-borne infections if sterile injecting equipment is not available or used. An injected mixture of cocaine and heroin , known as " speedball ", is a particularly dangerous combination, as the converse effects of the drugs actually complement each other, but may also mask the symptoms of an overdose. It has been responsible for numerous deaths, including celebrities such as comedians/actors John Belushi and Chris Farley , Mitch Hedberg , River Phoenix , grunge singer Layne Staley and actor Philip Seymour Hoffman . Experimentally, cocaine injections can be delivered to animals such as fruit flies to study
23864-454: The vagus nerve. Upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine (ACh) – the first known neurotransmitter. To identify neurotransmitters, the following criteria are typically considered: However, given advances in pharmacology , genetics , and chemical neuroanatomy ,
24021-597: The vapours can be inhaled . Cocaine stimulates the mesolimbic pathway in the brain. Mental effects may include an intense feeling of happiness , sexual arousal , loss of contact with reality , or agitation . Physical effects may include a fast heart rate , sweating, and dilated pupils . High doses can result in high blood pressure or high body temperature . Onset of effects can begin within seconds to minutes of use, depending on method of delivery, and can last between five and ninety minutes. As cocaine also has numbing and blood vessel constriction properties, it
24178-423: The vicinity of the emitting cell. Neurotransmitters represent another example of a paracrine signal. Some signaling molecules can function as both a hormone and a neurotransmitter. For example, epinephrine and norepinephrine can function as hormones when released from the adrenal gland and are transported to the heart by way of the blood stream. Norepinephrine can also be produced by neurons to function as
24335-426: The yeast Saccharomyces cerevisiae during mating , some cells send a peptide signal (mating factor pheromones ) into their environment. The mating factor peptide may bind to a cell surface receptor on other yeast cells and induce them to prepare for mating. Cell surface receptors play an essential role in the biological systems of single- and multi-cellular organisms and malfunction or damage to these proteins
24492-411: Was 14.6 minutes. Any damage to the inside of the nose is due to cocaine constricting blood vessels — and therefore restricting blood and oxygen/nutrient flow — to that area. Rolled up banknotes , hollowed-out pens , cut straws , pointed ends of keys, specialized spoons , long fingernails , and (clean) tampon applicators are often used to insufflate cocaine. The cocaine typically is poured onto
24649-480: Was first observed in the marine bacterium Aliivibrio fischeri , which produces light when the population is dense enough. The mechanism involves the production and detection of a signaling molecule, and the regulation of gene transcription in response. Quorum sensing operates in both gram-positive and gram-negative bacteria, and both within and between species. In slime molds , individual cells aggregate together to form fruiting bodies and eventually spores, under
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