5-HT receptor
Encyclopedia : 5 : 5H : 5HT : 5-HT receptor
In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT. 5-HT receptors are located on the cell membrane of nerve cells and other cell types in animals and mediate the effects of serotonin as the endogenous ligand and of a broad range of pharmaceutical and hallucinogenic drugs. With the exception of the 5-HT3 receptor, a ligand gated ion channel, all other 5-HT receptors are G protein coupled seven transmembrane (or heptahelical) receptors that activate an intracellular second messenger cascade.
- 5-HT1 receptors are Gi/Go coupled, mediating cellular effects through decreasing cellular levels of cyclic adenosine monophosphate (cAMP).
- 5-HT2 receptors are Gq/G11 coupled, mediating cellular effects through increasing cellular levels of inositol trisphosphate (IP3) and diacylglycerol (DAG). Three subtypes exist, namely 5-HT2A, 5-HT2B, and 5-HT2C (formerly called 5-HT1C).
- The 5-HT3 receptor is a ligand-gated Na+ and K+ cation channel, resulting in a direct plasma membrane depolarization.
- The 5-HT4 receptor is Gs coupled, mediating cellular effects through increasing cellular levels of cAMP.
- The 5-HT5A receptor is G protein coupled; the primary coupling appears to be through Gi/o, inhibiting adenylate cyclase activity. The 5-HT5B subtype exists, but has not been detected in humans.
- The 5-HT7 receptor is Gs coupled, mediating cellular effects through increasing cellular levels of cAMP.
Characterized 5-HT receptors
Within these general classes of 5-HT receptors, a number of specific types have been characterized:
| Receptor | Actions | Agonists | Antagonists |
|---|---|---|---|
| 5-HT1A | CNS: neuronal inhibition, behavioural effects (sleep, feeding, thermoregulation, anxiety) | buspirone | spiperone, methiothepin, ergotamine, yohimbine |
| 5-HT1B | CNS: presynaptic inhibition, behavioural effects; vascular: pulmonary vasoconstriction | ergotamine, sumatriptan | methiothepin, yohimbine, metergoline |
| 5-HT1D | CNS: locomotion; vascular: cerebral vasoconstriction | sumatriptan | methiothepin, yohimbine, metergoline, ergotamine |
| 5-HT2A | CNS: neuronal excitation, behavioural effects, learning; smooth muscle: contraction, vasoconstriction / dilatation; platelets: aggregation | α-methyl-5-HT, LSD (CNS) | ketanserin, cyproheptadine, pizotifen, LSD (PNS) |
| 5-HT2B | stomach: contraction | α-methyl-5-HT, LSD (CNS) | yohimbine, LSD (PNS) |
| 5-HT2C | CNS, choroid plexus: cerebrospinal fluid (CSF) secretion | α-methyl-5-HT, agomelatine, LSD (CNS) | mesulergine, agomelatine, LSD (PNS) |
| 5-HT3 | CNS, PNS: neuronal excitation, anxiety, emesis | 2-methyl-5-HT | metoclopramide (high doses), renzapride, ondansetron, alosetron, memantine |
| 5-HT4 | GIT, CNS: neuronal excitation, gastrointestinal motility | 5-methoxytryptamine, metoclopramide, renzapride, tegaserod | GR113808 |
| 5-HT5A | CNS (cortex, hippocampus, cerebellum): unknown | 5-carboxytryptamine; LSD (partial agonist) | unknown |
| 5-HT6 | CNS: unknown | LSD | SB271046[link] |
| 5-HT7 | CNS, GIT, blood vessels: unknown | 5-carboxytryptamine, LSD | methiothepin |
Note that there is no 5-HT1C receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT2 family of receptors and was redesignated as the 5-HT2C receptor.
Therapeutic modulation
Various drugs are used to modulate the 5-HT system including some antidepressants, anxiolytics, and antiemetics.References
External links
- [Serotonin Receptor Subtypes and Ligands] by R.A. Glennon, 2000
- [G Protein-Coupled Receptor Activation of 5-HT2A and other GPCRs. A hypothetical model of how these receptors work] by L.A. Rubenstein, 1997
- [5-HT Receptors and their Ligands] (tocris.com)
- [Basic Neurochemistry - Serotonin Receptors] (published 1999)
- [A. Wesolowska 2002, In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors, Pol. J. Pharmacol. 54 (4), 327-41] (free full text)
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