Desensitization of inositol 1,4,5-trisphosphate/Ca2+-induced Cl- currents by prolonged activation of G proteins in Xenopus oocytes.

The Journal of Biological Chemistry
M W QuickA M Aragay

Abstract

Expression of G protein alpha subunits of the Gq family with various G protein-coupled receptors induces activation of an inositol 1,4, 5-trisphosphate (IP3)/Ca2+-mediated Cl- conductance in Xenopus oocytes. Our present data show that two members of this family, the human Galpha16 subunit and the murine homologue Galpha15, can induce both activation and inhibition of these agonist-induced currents. Although extremely low amounts (10-50 pg) of injected Galpha16 subunit cRNA cause modest ( approximately 2-fold) enhancement of ligand-induced Cl- currents in oocytes co-injected with thyrotropin-releasing hormone (TRH) receptor cRNA 48 h postinjection, larger Galpha16 and Galpha15 cRNA injections cause >10-fold inhibition of TRH or 5HT2c receptor responses. The inhibition is analyzed in this study. The inhibited currents are recovered if various Gbetagamma subunit combinations are also expressed with the Galpha subunits. The constitutively active mutant, Galpha16Q212L, also causes a strong attenuation of the ligand-induced Cl- currents, but this inhibition is not recovered by co-expression of Gbetagamma subunits. These results indicate that the free Galpha subunit is responsible for the inhibitory signal. Although expression of TRH ...Continue Reading

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Citations

Mar 10, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J W Putney, R R McKay
Nov 8, 2001·Trends in Pharmacological Sciences·E Kostenis
Jun 1, 1997·Current Opinion in Neurobiology·K Mikoshiba
Jan 29, 2013·Neuroscience Letters·Jorge Mauricio Reyes-RuizRicardo Miledi
Oct 10, 2003·The Journal of Pharmacology and Experimental Therapeutics·Osamu MurasakiKohtaro Taniyama
Dec 4, 2004·Molecular Pharmacology·Petrine WellendorphHans Bräuner-Osborne
Feb 13, 1999·The Journal of Biological Chemistry·A M Aragay, M W Quick
Jul 12, 2003·Journal of Biomolecular Screening·Andrew M F LiuYung H Wong

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