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15 Cards in this Set
- Front
- Back
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What is the basic physiology of serotonin (5-HT)?
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5-HT is a widely distributed indoleethylamine formed from L-tryptophan, an amino acid derived from dietary protein.
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What regulates 5-HT's synthesis?
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Availability of tryptophan and the activity of tryptophan hydroxylase are thought to be the main factors that regulate 5-HT synthesis.
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Where is 5-HT synthesized?
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It is synthesized in chromaffin cells and neurons but not in platelets.
(Platelets take up 5HT from chromaffin cells in gut). Tryptophan is actively taken up into neurons, converted by tryptophan hydroxylase to 5-hydroxytryptophan, and then decarboxylated by a non-specific amino acid decarboxylase to 5-HT. Tryptophan hydroxylase can be selectively and irreversibly inhibited by p-chlorophenylalanine (PCPA). |
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What factors affect plasma content of serotonin?
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The plasma content varies with food intake and time of day.
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How is 5-HT stored?
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It is stored in neurons and chromaffin cells (> 90%) as a co-transmitter together with various peptides such as somatostatin, substance P or VIP. It is also stored in platelets (active carrier-mediated transport system similar to nerve endings).
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How is 5-HT degraded?
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Monoamine oxidase (MAO) produces 5-hydroxyindoleacetaldehyde (5-HIAA) which is then excreted in the urine and serves as an indicator of 5-HT production in the body. (e.g., diagnosis of carcinoid syndrome)
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What is the role of 5-HT in the GI system?
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5-HT1B receptors -> initiation of secretory & peristaltic reflexes;
presynaptic 5-HT4 receptors amplifies neurotransmission in some enteric neurons -> prokinetic activity in the gut & may regulate colonic motility; |
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How does 5-HT affect blood vessels?
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Causes:
constriction of large peripheral vessels (5-HT2A); constriction of large intracranial vessels (5-HT1); dilatation of arterioles partly by release of NO from endothelial cells and partly by inhibiting NE release from sympathetic nerve terminals. 5-HT administration IV -> initial BP increase due to the constriction of large vessels, then fall, due to arteriolar dilation. |
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How does 5-HT affect platelets?
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It causes plt aggregation by acting on 5-HT2A receptors, and the platelets that collect in the vessel release further 5-HT.
If the endothelium is intact, 5-HT release from adherent platelets causes vasodilatation, which helps to sustain blood flow; if it is damaged (e.g. by atherosclerosis), 5-HT causes constriction and impairs blood flow further. These effects of platelet-derived 5-HT are thought to be important in vascular disease. |
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How does 5-HT affect nerve endings?
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5-HT stimulates nociceptive (pain-mediating) sensory nerve endings, an effect mediated mainly by 5-HT3 receptors.
If injected into the skin, 5-HT causes pain; when given systemically, it elicits a variety of autonomic reflexes through stimulation of afferent fibres in the heart and lungs, which further complicate the cardiovascular response. Nettle stings contain 5-HT among other mediators. |
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How does 5-HT affect central nervous system?
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5-HT excites some neurons and inhibits others; it may also act presynaptically to inhibit transmitter release from nerve terminals.
Different receptor subtypes and different membrane mechanisms mediate these effects. |
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What receptor type are 5-HT receptors?
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They are all GPCR, except 5-HT3, which is a a ligand-gated cation channel.
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How many serotonin receptor types are there?
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Seven - 5-HT1-7 with further subtypes of of A-D for 5-HT1 & 5-HT2.
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Where are 5-HT1 receptors found? & what are their effects?
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5-HT1 receptors (all subtypes) are mainly found in the CNS & blood vessels (5-HT1D).
Neural inhibition & vasoconstriction. They act by inhibiting adenylate cyclase. |
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Where are 5-HT2 receptors found? & what are their effects?
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Occurs in CNS & many peripheral sites (blood vessels, plts & autonomic neurons). Neuronal & smooth muscle effects are excitory. Some blood vessels dilate via NO from endotheliun release.
5-HT2 act thru PLC/IP3 pathway. |
