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• W1999469237 endingPage "1363" @default.
• W1999469237 startingPage "1355" @default.
• W1999469237 abstract "Two classical neurotransmitters, 5-hydroxytryptamine (5-HT) and GABA, coexist in neurons of the medulla oblongata, and activation of 5-HT receptors modulates GABAA 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 GABAA receptors in Xenopus oocytes coexpressing both types of receptors 5-HT2C receptors caused a approximately 60% decrease in the GABAA receptor Emax without affecting the EC50 or Hill coefficient. Intracellular microinjection of 500 microM BAPTA blocked, whereas microinjection of inositol 1,4,5-triphosphate mimicked the inhibitory action of 5-HT2C receptors. The inhibition was independent of the GABAA receptors subunit composition; receptors containing alpha 2 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, GABAA 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 GABAA receptors with different subunit compositions, suggest that protein kinases or serine/threonine phosphatases are not involved in this GABAA receptor modulatory process. Thus, we propose that 5-HT2C receptors inhibit GABAA receptors by a Ca(2+)-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 anti-anxiety actions of 5-HT2 receptor antagonists." @default.
• W1999469237 created "2016-06-24" @default.
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• W1999469237 date "1996-01-01" @default.
• W1999469237 modified "2023-10-13" @default.
• W1999469237 title "Modulation of GABA A Receptor Function by G Protein-coupled 5-HT 2C Receptors" @default.
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• W1999469237 doi "https://doi.org/10.1016/s0028-3908(96)00084-6" @default.
• W1999469237 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9014152" @default.
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