5-HT receptor

From Wikipedia, the free encyclopedia

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 including smooth muscle in animals, and mediate the effects of serotonin as the endogenous ligand and of a broad range of pharmaceutical and hallucinogenic drugs. All 5-HT receptors reduce cyclic adenosine monophosphate (cAMP).

Contents 1 Classification 1.1 Families 1.2 Specific proteins/genes 2 Therapeutic modulation 3 References 4 External links

[edit] Classification

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.

[edit] Families

• 5-HT₁ receptors are G_i/G_o coupled, mediating cellular effects through decreasing cellular levels of cyclic adenosine monophosphate (cAMP).

• 5-HT₂ receptors are G_q/G₁₁ coupled, mediating cellular effects through increasing cellular levels of inositol trisphosphate (IP₃) and diacylglycerol (DAG). Three subtypes exist, namely 5-HT_2A, 5-HT_2B, and 5-HT_2C (formerly called 5-HT_1C).

• 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 G_s coupled, mediating cellular effects through increasing cellular levels of cAMP.

• The 5-HT_5A receptor is G protein coupled; the primary coupling appears to be through Gi/o, inhibiting adenylate cyclase activity.^[1] The 5-HT_5B subtype exists, but has not been detected in humans.

• The 5-HT₇ receptor is G_s coupled, mediating cellular effects through increasing cellular levels of cAMP.

[edit] Specific proteins/genes

Within these general classes of 5-HT receptors, a number of specific types have been characterized:

Summary of characterized 5-HT receptors, with selected agonist/antagonist agents

Receptor	Actions	Agonists	Antagonists
5-HT1A	CNS: neuronal inhibition, behavioural effects (sleep, feeding, thermoregulation, aggression, 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), DOI	Nefazodone, trazodone, mirtazapine, ketanserin, cyproheptadine, pizotifen, LSD (PNS)
5-HT2B	stomach: contraction	α-methyl-5-HT, LSD (CNS), DOI	yohimbine, LSD (PNS)
5-HT2C	CNS, choroid plexus: cerebrospinal fluid (CSF) secretion	α-methyl-5-HT, agomelatine, LSD (CNS), DOI	mesulergine, agomelatine, LSD (PNS)
5-HT3	CNS, PNS: neuronal excitation, anxiety, emesis	2-methyl-5-HT	metoclopramide (high doses), renzapride, ondansetron, alosetron, mirtazapine, 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)[1]	unknown
5-HT6	CNS: unknown	LSD	SB271046[1]
5-HT7	CNS, GIT, blood vessels: unknown	5-carboxytryptamine, LSD	methiothepin

Note that there is no 5-HT_1C 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-HT_2C receptor.

[edit] Therapeutic modulation

Various drugs are used to modulate the 5-HT system including some antidepressants, anxiolytics, and antiemetics.

[edit] References

1. ^ ^{a b} D.L. Nelson (2004). "5-HT5 receptors". Curr. Drug Targets CNS Neurol. Disord. 3 (1): 53-58. PMID 14965244. 

[edit] External links

• IUPHAR GPCR Database - 5-HT Receptors
• 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)
• MeSH Serotonin+Receptors