Modulation of GABA(A) receptor function by G protein-coupled 5-HT2C receptors

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dc.contributor.authorHuidobroToro, JP
dc.contributor.authorValenzuela, CF
dc.contributor.authorHarris, RA
dc.date.accessioned2025-01-21T01:34:13Z
dc.date.available2025-01-21T01:34:13Z
dc.date.issued1996
dc.description.abstractTwo classical neurotransmitters, 5-hydroxytryptamine (5-HT) and GABA, coexist in neurons of the medulla oblongata, and activation of 5-HT receptors modulates GABA(A) receptor function in neurons of the ventral tegmental area, substantia nigra and cerebellum. We now report that activation of 5-HT2C receptors produces a long-lasting (20-90 min) inhibition of GABA(A) receptors in Xenopus oocytes coexpressing both types of receptors. 5-HT2C receptors caused a similar to 60% decrease in the GABA(A) receptor E(max) without affecting the EC(50) or Hill coefficient. Intracellular microinjection of 500 mu M BAPTA blocked, whereas microinjection of inositol 1,4,5-triphosphate mimicked the inhibitory action of 5-HT2C receptors. The inhibition was independent of the GABA(A) receptors subunit composition; receptors containing alpha 2 beta 1, alpha 1 beta 1, alpha 1 beta 1 gamma 2L, and alpha 2 beta 1 gamma 2S were inhibited to the same extent by 5-HT2C receptor activation. Moreover, GABA(A) receptors composed of wild-type alpha 2 plus mutant beta 1((S409A)) subunits were inhibited to the same extent as wild-type receptors. The nonspecific protein kinase inhibitor, staurosporine, and the inhibitor of serine/threonine protein phosphatases, calyculin A, did not block the inhibitory effects of 5-HT2C receptors. The results with these inhibitors, taken together with those obtained with GABA(A) receptors with different subunit compositions, suggest that protein kinases or serine/threonine phosphatases are not involved in this GABA(A) receptor modulatory process. Thus, we propose that 5-HT2C receptors inhibit GABA(A) receptors by a Ca2+-dependent, but phosphorylation independent, mechanism and that 5-HT and GABA may act as cotransmitters to regulate neuronal activity. Furthermore, disruption of the cross-talk between these receptors may play a role in the antianxiety actions of 5-HT2 receptor antagonists. Copyright (C) 1996 Elsevier Science Ltd.
dc.description.funderNIAAA NIH HHS
dc.fuente.origenWOS
dc.identifier.eissn1873-7064
dc.identifier.issn0028-3908
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/97530
dc.identifier.wosidWOS:A1996WC18200025
dc.issue.numero9-10
dc.language.isoen
dc.pagina.final1363
dc.pagina.inicio1355
dc.revistaNeuropharmacology
dc.rightsacceso restringido
dc.subjectGABA(A) receptors
dc.subject5-hydroxytryptamine
dc.subject5-HT2C receptors
dc.subjectXenopus oocytes
dc.subjectphosphorylation
dc.subjectG protein
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleModulation of GABA(A) receptor function by G protein-coupled 5-HT2C receptors
dc.typeartículo
dc.volumen35
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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