5-HT5A receptor

5-HT5A receptor

5-hydroxytryptamine (serotonin) receptor 5A, G protein-coupled
Identifiers
Symbols  ; 5-HT5A
External IDs IUPHAR: ChEMBL: GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein that in humans is encoded by the HTR5A gene.[1][2]

Function

The gene described in this record is a member of 5-hydroxytryptamine receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G proteins, negatively influencing cAMP levels via Gi and Go.[3] This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization.[1]

Rodents have been shown to possess two functional 5-HT5 receptor subtypes, 5-HT5A and 5-HT5B,[4] however while humans possess a gene coding for the 5-HT5B subtype, its coding sequence is interrupted by stop codons, making the gene non-functional, and so only the 5-HT5A subtype is expressed in human brain.[5]

It also appears to serve as an presynaptic serotonin autoreceptor.[6]

Clinical significance

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects.[1]

Selective Ligands

Few highly selective ligands are commercially available for the 5-HT5A receptor. When selective activation of this receptor is desired in scientific research, the non-selective serotonin receptor agonist 5-Carboxamidotryptamine can be used in conjunction with selective antagonists for its other targets (principally 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT7). Research in this area is ongoing.[7][8]

Agonists

  • Another ligand that has been recently disclosed is shown below, claimed be a selective 5-HT5A agonist with Ki = 124 nM.[10]

Antagonists

See also

References

  1. ^ a b c "Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A". 
  2. ^ Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (December 1994). "Cloning and characterisation of the human 5-HT5A serotonin receptor". FEBS Lett. 355 (3): 242–6.  
  3. ^ Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (November 1998). "The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells". Eur. J. Pharmacol. 361 (2-3): 299–309.  
  4. ^ Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R (March 1993). "Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization". Mol. Pharmacol. 43 (3): 313–9.  
  5. ^ Nelson DL (February 2004). "5-HT5 receptors". Curr Drug Targets CNS Neurol Disord 3 (1): 53–8.  
  6. ^ Thomas DR, Soffin EM, Roberts C, Kew JN, de la Flor RM, Dawson LA, Fry VA, Coggon SA, Faedo S, Hayes PD, Corbett DF, Davies CH, Hagan JJ (September 2006). "SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), a novel 5-ht5A receptor-selective antagonist, enhances 5-HT neuronal function: Evidence for an autoreceptor role for the 5-ht5A receptor in guinea pig brain". Neuropharmacology 51 (3): 566–77.  
  7. ^ Wesołowska A (2002). "In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors". Pol J Pharmacol 54 (4): 327–41.  
  8. ^ Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L (January 2008). "Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration". Bioorg. Med. Chem. Lett. 18 (1): 262–6.  
  9. ^ Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (August 2005). "Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro". Brain Res. Mol. Brain Res. 138 (2): 191–7.  
  10. ^ Garcia-Ladona, Francisco Javier; Szabo, Laszlo; Steiner, Gerd; Hofmann, Hans-Peter (2004-06-15). "Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances". Patent US 6750221. 
  11. ^ Wu J, Li Q, Bezprozvanny I (2008). "Evaluation of Dimebon in cellular model of Huntington's disease". Mol Neurodegener 3 (1): 15.  

External links

  • "5a"5-ht. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.