5-hydroxytryptamine receptor 5A

From DrugPedia: A Wikipedia for Drug discovery

Contents 1 Description 2 General Characterstics 2.1 Source Organism 2.2 Taxomomy 2.3 Subcellular Localization 3 Developmental Stage 3.1 Similarity 4 Function 5 Clinical signficance 6 Ligands 6.1 Antagonists 7 See also 8 External links 9 References

Description

5-hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein which in humans is encoded by the HTR5A gene.<ref name="entrez">Template:Cite web</ref><ref name="pmid7988681">Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (December 1994). "[h 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. </ref>

General Characterstics

Source Organism

Cavia porcellus (Guinea pig).

Taxomomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia;Hystricognathi; Caviidae; Cavia.

Subcellular Localization

Membrane (By similarity).

Developmental Stage

Similarity

Belongs to the G-protein coupled receptor 1 family.

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 G_i and G_o.<ref name="pmid9865521">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. PMID 9865521. </ref> This protein has been shown to function in part through the regulation of intracellular Ca²⁺ mobilization.<ref name="entrez"/>

Rodents have been shown to possess two functional 5-HT₅ receptor subtypes, 5-HT_5A and 5-HT_5B,<ref name="pmid8450829">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. </ref> however while humans possess a gene coding for the 5-HT_5B subtype, its coding sequence is interrupted by stop codons making the gene non-functional, and so only the 5-HT_5A subtype is expressed in human brain.<ref name="pmid14965244">Nelson DL (February 2004). "5-HT5 receptors". Curr Drug Targets CNS Neurol Disord 3 (1): 53–8. PMID 14965244. </ref>

Clinical signficance

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects.<ref name="entrez"/>

Categories:Receptors Template:Wrongtitle Template:PBB

Ligands

Few highly selective ligands are commercially available for the 5-HT_5A 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-HT_1A, 5-HT_1B, 5-HT_1D and 5-HT₇). Research in this area is ongoing.<ref name="pmid12523486">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. </ref><ref name="pmid18023344">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. </ref>

Agonists

• Valerenic acid, a component of valerian, has been shown to act as a 5HT_5A partial agonist.<ref name="pmid15921820">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. </ref>

• Another ligand which has been recently disclosed is shown below, claimed be a selective 5-HT_5A agonist with K_i = 124 nM.<ref name = "US6750221" >Template:Citation</ref>

Image:DE19900637A1 5HT5A ligand.png

Antagonists

• SB-699,551

See also

• 5-HT receptor

External links

• Template:Cite web

References

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