5-hydroxytryptamine 1A receptor

From DrugPedia: A Wikipedia for Drug discovery

Contents 1 Description 2 Source Organism 3 Taxomomy 4 Subcellular Localization 5 Developmental Stage 6 Similarity 7 Post translational Modification 8 Ligands 9 Genetics 10 Function 11 External links 12 References

[edit] Description

5-hydroxytryptamine (serotonin) receptor 1A is a 5-HT₁ receptor. HTR1A denotes the human gene encoding it.<ref name="pmid2591972">Gilliam TC, Freimer NB, Kaufmann CA, Powchik PP, Bassett AS, Bengtsson U, Wasmuth JJ (November 1989). "Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia". Genomics 5 (4): 940–4. PMID 2591972. </ref><ref name="entrez">Template:Cite web</ref> 5-HT_1A acts on the CNS, where it induces neuronal inhibition and controls behaviour, such as sleep, feeding, thermoregulation, aggression, anxiety.

[edit] Source Organism

Canis familiaris (Dog).

[edit] Taxomomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae;Canis.

[edit] Subcellular Localization

Cell membrane; multi-pass membrane protein.

[edit] Developmental Stage

[edit] Similarity

Belongs to the G-protein coupled receptor 1 family.

[edit] Post translational Modification

[edit] Ligands

The distribution of 5-HT_1A receptors in the human brain may be imaged with the positron emission tomography using the radioligand [¹¹C]WAY-100635.<ref name="pmid7498295">Pike VW, McCarron JA, Lammerstma AA, Hume SP, Poole K, Grasby PM, Malizia A, Cliffe IA, Fletcher A, Bench CJ (1995). "First delineation of 5-HT_1A receptors in human brain with PET and [¹¹C]WAY-100635". Eur. J. Pharmacol. 283 (1-3): R1–3. doi:10.1016/0014-2999(95)00438-Q. PMID 7498295. </ref> For example, one study has found increased 5-HT_1A binding in type 2 diabetes.<ref name="pmid11814436">Price JC, Kelley DE, Ryan CM, Meltzer CC, Drevets WC, Mathis CA, Mazumdar S, Reynolds CF (2002). "Evidence of increased serotonin-1A receptor binding in type 2 diabetes: a positron emission tomography study". Brain Res. 927 (1): 97–103. doi:10.1016/S0006-8993(01)03297-8. PMID 11814436. </ref> Another PET study found a negative correlation between amount of 5-HT_1A binding in the raphe nuclei, hippocampus and neocortex and a self reported tendency to have spiritual experiences.<ref name="pmid14594742">Borg J, Andrée B, Soderstrom H, Farde L (November 2003). "The serotonin system and spiritual experiences". Am J Psychiatry 160 (11): 1965–9. doi:10.1176/appi.ajp.160.11.1965. PMID 14594742. </ref>

Labeled with tritium, WAY-100635 may also be used in autoradiography.<ref name="pmid9152998">Burnet PW, Eastwood SL, Harrison PJ (1997). "[³H]WAY-100635 for 5-HT_1A receptor autoradiography in human brain: a comparison with [³H]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia". Neurochem. Int. 30 (6): 565–574. doi:10.1016/S0197-0186(96)00124-6. PMID 9152998. </ref>

Agonists

Antagonists

buspirone Aripiprazole 5-CT 8-OH-DPAT flesinoxan LSD MDMA (speculated)<ref>Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS.. "A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy").". </ref> psilocin U-92016A<ref name="pmid7965808">McCall RB, Romero AG, Bienkowski MJ, Harris DW, McGuire JC, Piercey MF, Shuck ME, Smith MW, Svensson KA, Schreur PJ, et al. (1994). "Characterization of U-92016A as a selective, orally active, high intrinsic activity 5-hydroxytryptamine1A agonist.". J. Pharmacol. Exp. Ther. 271 (2): 875-883. PMID 7965808. </ref> vilazodone xaliproden

ergotamine lecozotan methiothepin MPPF pindolol robalzotan spiperone WAY-100135 WAY-100635<ref name="pmid8768728">Fornal CA, Metzler CW, Gallegos RA, Veasey SC, McCreary AC, Jacobs BL (1996). "WAY-100635, a potent and selective 5-hydroxytryptamine1A antagonist, increases serotonergic neuronal activity in behaving cats: comparison with (S)-WAY-100135". J. Pharmacol. Exp. Ther. 278 (2): 752–62. PMID 8768728. </ref> yohimbine

[edit] Genetics

The receptor is coded by the HTR1A gene. There are several human polymorphisms associated with this gene. A 2007 review listed 27 single nucleotide polymorphisms (SNP).<ref name="DragoA20075HT1A">Drago A, Ronchi DD, Serretti A (August 2008). "5-HT_1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies". Int. J. Neuropsychopharmacol. 11 (5): 701–21. doi:10.1017/S1461145707008218. PMID 18047755. </ref> The most investigated SNPs are C(-1019)G (rs6295) (C-1018G,<ref name="pmid10412191">Wu S, Comings DE (June 1999). "A common C-1018G polymorphism in the human 5-HT_1A receptor gene". Psychiatr. Genet. 9 (2): 105–6. doi:10.1097/00041444-199906000-00010. PMID 10412191. </ref> Ile28Val (rs1799921), Arg219Leu (rs1800044) and Gly22Ser (rs1799920).<ref name="DragoA20075HT1A"/> Some of the other SNPs are Pro16Leu, Gly272Asp and the synonymous polymorphism G294A (rs6294).

The gene variants have been studied in relation to psychiatric disorders with no definitive results.<ref name="DragoA20075HT1A"/>

[edit] Function

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity (By similarity)

[edit] External links

• Template:Cite web

[edit] References

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