5-HT receptor

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

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.[1] 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. 5-HT receptors affect the release and activity of other neurotransmitters such as glutamate, dopamine and GABA. 5-HT2A receptors increase the activity of glutamate in many areas of the brain, while some other serotonin receptors have the effect of suppressing glutamate. Increased stimulation of 5-HT2A receptors seem to oppose the therapeutic actions of increased stimulation of other serotonin receptors in anti-depressant and anxiolytic treatments.[2]

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.

Families

Family Type Mechanism
5-HT1 Gi/Go coupled decreasing cellular levels of cAMP
5-HT2 Gq/G11 coupled increasing cellular levels of inositol trisphosphate (IP3) and diacylglycerol (DAG)
5-HT3 ligand-gated Na+ and K+ cation channel depolarizing plasma membrane
5-HT4 Gs coupled increasing cellular levels of cAMP
5-HT5A G protein coupled; the primary coupling appears to be through Gi/o inhibiting adenylate cyclase activity.[3]
5-HT6 Gs coupled increasing cellular levels of cAMP
5-HT7 Gs coupled increasing cellular levels of cAMP

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 high affinity agonist and antagonist ligands
Receptor Gene Actions Agonists Antagonists
5-HT1A HTR1A
  • CNS: neuronal inhibition, behavioural effects (sleep, feeding, thermoregulation, aggression, anxiety)
5-HT1B HTR1B
5-HT1D HTR1D
  • 5-(Nonyloxy)tryptamine,[4]
  • sumatriptan
  • methiothepin
  • yohimbine
  • metergoline
  • ergotamine
5-HT1E HTR1E
5-HT1F HTR1F
5-HT2A HTR2A
5-HT2B HTR2B
  • stomach: contraction
5-HT2C HTR2C
5-HT3 HTR3A, HTR3B
  • CNS, PNS: neuronal excitation, anxiety, emesis
  • 2-methyl-5-HT
5-HT4 HTR4
  • GIT: gastrointestinal motility
  • CNS: neuronal excitation, learning, memory
  • GR113808
  • Piboserod
5-HT5A HTR5A unknown
5-HT6 HTR6
  • CNS: unknown
  • LSD
SB271046[6]
5-HT7 HTR7
  • CNS, GIT, blood vessels: unknown
  • 5-carboxytryptamine
  • LSD

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, antiemetics, antipsychotics and anti-migraine agents.

External links

References

  1. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994). "International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin)". Pharmacol. Rev. 46 (2): 157–203. PMID 7938165. 
  2. Marek GJ, Carpenter LL, McDougle CJ, Price LH (2003). "Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders". Neuropsychopharmacology. 28 (2): 402–12. PMID 12589395. doi:10.1038/sj.npp.1300057. 
  3. 3.0 3.1 Nelson DL (2004). "5-HT5 receptors". Current drug targets. CNS and neurological disorders. 3 (1): 53–8. PMID 14965244. 
  4. Glennon RA, Hong SS, Dukat M, Teitler M, Davis K (1994). "5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT1D beta serotonin receptor agonist". J. Med. Chem. 37 (18): 2828–30. PMID 8071931. doi:10.1021/jm00044a001. 
  5. Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.  Page 187
  6. "Target Schizophrenia - Possible future developments". The Association of the British Pharmaceutical Industry. Retrieved 2008-04-11. 

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