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VMAT Inhibitors
The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membranes of synaptic vesicles of synapse, presynaptic neurons. It transports monoamine neurotransmitters – such as dopamine, serotonin, norepinephrine, epinephrine, and histamine – into the Vesicle (biology and chemistry), vesicles, which release the neurotransmitters into synapses as chemical messages to postsynaptic neurons. VMATs utilize a Electrochemical gradient, proton gradient generated by V-ATPases in vesicle membranes to power monoamine import. Pharmaceutical drugs that target VMATs have possible applications for many conditions, leading to a plethora of biological research, including hypertension, Drug-addiction, drug addiction, psychiatric disorders, Parkinson's disease, and other neurological disorders. Many drugs that target VMATs act as inhibitors and alter the kinetics of the protein. Much research regarding the effects of altered VMATs on biological systems is still ongoing. ...
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Transport Protein
A transport protein (variously referred to as a transmembrane pump, transporter, escort protein, acid transport protein, cation transport protein, or anion transport protein) is a protein that serves the function of moving other materials within an organism. Transport proteins are vital to the growth and life of all living things. There are several different kinds of transport proteins. Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is, they exist within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion (i.e., passive transport) or active transport. These mechanisms of movement are known as carrier-mediated transport. Each carrier protein is designed to recognize only one substance or one group of very similar substances. Researc ...
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Adrenaline
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and by a small number of neurons in the medulla oblongata. It plays an essential role in the fight-or-flight response by increasing blood flow to muscles, heart output by acting on the SA node, pupil dilation response, and blood sugar level. It does this by binding to alpha and beta receptors. It is found in many animals, including humans, and some single-celled organisms. It has also been isolated from the plant ''Scoparia dulcis'' found in Northern Vietnam. Medical uses As a medication, it is used to treat several conditions, including allergic reaction anaphylaxis, cardiac arrest, and superficial bleeding. Inhaled adrenaline may be used to improve the symptoms of croup. It may also be used for asthma when other treatments are not eff ...
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Enterochromaffin Cells
Enterochromaffin (EC) cells (also known as Kulchitsky cells) are a type of enteroendocrine cell, and neuroendocrine cell. They reside alongside the epithelium lining the lumen of the digestive tract and play a crucial role in gastrointestinal regulation, particularly intestinal motility and secretion. They were discovered by Nikolai Kulchitsky. EC cells modulate neuron signalling in the enteric nervous system (ENS) via the secretion of the neurotransmitter serotonin and other peptides. As enteric afferent and efferent nerves do not protrude into the intestinal lumen, EC cells act as a form of sensory transduction. Serotonin in the ENS acts in synergy with other digestive hormones to regulate sensory and motor gastrointestinal reflexes. EC cells respond to both chemical and neurological stimuli. They are also reactive to mechanosensation, which is the case in the peristaltic reflex of the gut, and can be stimulated by a bolus moving through the bowel. Upon activation, EC cells rel ...
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Chromaffin Cell
Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to stress, monitoring carbon dioxide and oxygen concentrations in the body, maintenance of respiration and the regulation of blood pressure. They are in close proximity to pre-synaptic sympathetic ganglia of the sympathetic nervous system, with which they communicate, and structurally they are similar to post-synaptic sympathetic neurons. In order to activate chromaffin cells, the splanchnic nerve of the sympathetic nervous system releases acetylcholine, which then binds to nicotinic acetylcholine receptors on the adrenal medulla. This causes the release of catecholamines. The chromaffin cells release catecholamines: ~80% of adrenaline ( epinephrine) and ~20% of noradrenaline (norepinephrine) into systemic circulation for systemic effects on multiple org ...
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Neuroendocrine Cell
Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules ( hormones) into the blood. In this way they bring about an integration between the nervous system and the endocrine system, a process known as neuroendocrine integration. An example of a neuroendocrine cell is a cell of the adrenal medulla (innermost part of the adrenal gland), which releases adrenaline to the blood. The adrenal medullary cells are controlled by the sympathetic division of the autonomic nervous system. These cells are modified postganglionic neurons. Autonomic nerve fibers lead directly to them from the central nervous system. The adrenal medullary hormones are kept in vesicles much in the same way neurotransmitters are kept in neuronal vesicles. Hormonal effects can last up to ten times longer than those of neurotransmitters. Sympathetic nerve fiber impulses sti ...
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VMAT2
The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from cellular cytosol into synaptic vesicles. In nigrostriatal pathway and mesolimbic pathway dopamine-releasing neurons, SLC18A2 function is also necessary for the vesicular release of the neurotransmitter GABA. Binding sites and ligands SLC18A2 is believed to possess at least two distinct binding sites, which are characterized by tetrabenazine (TBZ) and reserpine binding to the transporter. Amphetamine (TBZ site) and methamphetamine (reserpine site) bind at distinct sites on SLC18A2 to inhibit its function. SLC18A2 inhibitors like tetrabenazine and reserpine reduce the concentration of monoamine neurotransmitters in the synaptic cleft by inhibiting uptake ...
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VMAT1
Vesicular monoamine transporter 1 (VMAT1) also known as chromaffin granule amine transporter (CGAT) or solute carrier family 18 member 1 (SLC18A1) is a protein that in humans is encoded by the ''SLC18A1'' gene. VMAT1 is an integral membrane protein, which is embedded in synaptic vesicles and serves to transfer monoamines, such as norepinephrine, epinephrine, dopamine, and serotonin, between the cytosol and synaptic vesicles. SLC18A1 is an isoform of the vesicular monoamine transporter. Discovery The idea that there must be specific transport proteins associated with the uptake of monoamines and acetylcholine into vesicles developed due to the discovery of specific inhibitors which interfered with monoamine neurotransmission and also depleted monoamines in neuroendocrine tissues. VMAT1 and VMAT2 were first identified in rats upon cloning cDNAs for proteins which gave non-amine accumulating recipient cells the ability to sequester monoamines. Subsequently, human VMATs were cloned ...
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Denaturation (biochemistry)
In biochemistry, denaturation is a process in which proteins or nucleic acids lose the quaternary structure, tertiary structure, and secondary structure which is present in their native state, by application of some external stress or compound such as a strong acid or base, a concentrated inorganic salt, an organic solvent (e.g., alcohol or chloroform), agitation and radiation or heat. If proteins in a living cell are denatured, this results in disruption of cell activity and possibly cell death. Protein denaturation is also a consequence of cell death. Denatured proteins can exhibit a wide range of characteristics, from conformational change and loss of solubility to aggregation due to the exposure of hydrophobic groups. The loss of solubility as a result of denaturation is called ''coagulation''. Denatured proteins lose their 3D structure and therefore cannot function. Protein folding is key to whether a globular or membrane protein can do its job correctly; it must be ...
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Reserpine
Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces mortality of people with hypertension. Although the use of reserpine as a solo drug has declined since it was first approved by the FDA in 1955, the combined use of reserpine and a thiazide diuretic or vasodilator is still recommended in patients who do not achieve adequate lowering of blood pressure with first-line drug treatment alone. The reserpine-hydrochlorothiazide combo pill was the 17th most commonly prescribed of the 43 combination antihypertensive pills available In 2012. The antihypertensive actions of reserpine are largely due to its antinoradrenergic effects, which are a result of its ability to deplete catecholamines (among other monoamine neurotransmitters) from peripheral sympathetic nerve endings. These substances are no ...
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Arvid Carlsson
Arvid Carlsson (25 January 1923 – 29 June 2018) was a Swedish neuropharmacologist who is best known for his work with the neurotransmitter dopamine and its effects in Parkinson's disease. For his work on dopamine, Carlsson was awarded the Nobel Prize in Physiology or Medicine in 2000, together with Eric Kandel and Paul Greengard. Early life and education Carlsson was born on 25 January 1923 in Uppsala, Sweden, one of four siblings. His family moved to Lund after his father became a history professor at Lund University. Although his two older siblings followed their father's career path, he instead chose to study medicine at Lund, beginning in 1941. In 1944, he participated in the task of examining prisoners of Nazi concentration camps, whom Swedish aristocrat Folke Bernadotte had managed to bring to Sweden, which was neutral during World War II. He received his MD and PhD in pharmacology in 1951. Career In 1951, Carlsson became an associate professor at Lund University. ...
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Secretory Vesicles
440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mechanism of cell secretion is via secretory portals at the plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structures embedded in the cell membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell. Secretion in bacterial species means the transport or translocation of effector molecules for example: proteins, enzymes or toxins (such as cholera toxin in pathogenic bacteria e.g. ''Vibrio cholerae'') from across the interior (cytoplasm or cytosol) of a bacterial cell to its exterior. Secretion is a very important mechanism in bacterial functioning and operation in their natural surrounding environment for adaptation and survival. In eukaryotic cells Me ...
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Nils-Åke Hillarp
Nils-Åke Hillarp (4 July 1916 – 17 March 1965) was a Swedish scientist and a prominent force in research on the brain's monoamines. Biography Hillarp was the son of merchant Nils Bengtsson and Hulda, former Johansson, and the brother of Rut Hillarp, a novelist. He became Doctor of Medical Science (equivalent to a Ph.D.) in 1946. He was appointed assistant and later associate professor of Histology at the University of Lund (1946–1962). The Swedish Medical Research Council enabled him to spend 1960 to 1962 in research at the Department of Pharmacology, University of Gothenburg, then in 1962 he became full professor of histology at the Karolinska Institute in Stockholm, Sweden where he remained until his death in 1965. Research Hillarp's research on the terminal fiber system of the autonomic nervous system was of significant importance, as was his work on the mechanics of nerve impulse transmission. Perhaps his most important research was with Bengt Falck, as they together dev ...
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