5-HT5A receptor

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5-hydroxytryptamine (serotonin) receptor 5A, G protein-coupled
Identifiers
Symbols HTR5A ; 5-HT5A
External IDs OMIM601305 MGI96283 HomoloGene22461 IUPHAR: 5-ht5a ChEMBL: 3426 GeneCards: HTR5A Gene
RNA expression pattern
PBB GE HTR5A 221362 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3361 15563
Ensembl ENSG00000157219 ENSMUSG00000039106
UniProt P47898 P30966
RefSeq (mRNA) NM_024012 NM_008314
RefSeq (protein) NP_076917 NP_032340
Location (UCSC) Chr 7:
154.86 – 154.88 Mb
Chr 5:
27.84 – 27.86 Mb
PubMed search [1] [2]

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

Function[edit]

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[edit]

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[edit]

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[edit]

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

DE19900637A1 5HT5A ligand.png

Antagonists[edit]

See also[edit]

References[edit]

  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. doi:10.1016/0014-5793(94)01209-1. PMID 7988681. 
  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. doi:10.1016/S0014-2999(98)00744-4. PMID 9865521. 
  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. PMID 8450829. 
  5. ^ Nelson DL (February 2004). "5-HT5 receptors". Curr Drug Targets CNS Neurol Disord 3 (1): 53–8. doi:10.2174/1568007043482606. PMID 14965244. 
  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. doi:10.1016/j.neuropharm.2006.04.019. PMID 16846620. 
  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. PMID 12523486. 
  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. doi:10.1016/j.bmcl.2007.10.078. PMID 18023344. 
  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. doi:10.1016/j.molbrainres.2005.04.009. PMID 15921820. 
  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. US. 
  11. ^ Wu J, Li Q, Bezprozvanny I (2008). "Evaluation of Dimebon in cellular model of Huntington's disease". Mol Neurodegener 3 (1): 15. doi:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977. 

External links[edit]

  • "5-ht5a". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

Further reading[edit]

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