PT - JOURNAL ARTICLE AU - Nathalie Macrez AU - Jean-Luc Morel AU - Jean Mironneau TI - Specific Gα<sub>11</sub>β<sub>3</sub>γ<sub>5</sub>Protein Involvement in Endothelin Receptor-Induced Phosphatidylinositol Hydrolysis and Ca<sup>2+</sup> Release in Rat Portal Vein Myocytes DP - 1999 Apr 01 TA - Molecular Pharmacology PG - 684--692 VI - 55 IP - 4 4099 - http://molpharm.aspetjournals.org/content/55/4/684.short 4100 - http://molpharm.aspetjournals.org/content/55/4/684.full SO - Mol Pharmacol1999 Apr 01; 55 AB - In this study, we identified the receptor subtype activated by endothelin-1 (ET-1) and the subunit composition of the G protein coupling this receptor to increase in cytosolic Ca2+concentration in rat portal vein myocytes. We used intranuclear antisense oligonucleotide injection to selectively inhibit the expression of G protein subunits. We show here that the endothelin receptor subtype A (ETA)-mediated increase in cytosolic Ca2+ concentration was mainly dependent on Ca2+ release from the intracellular store. ETAreceptor-mediated Ca2+ release was selectively inhibited by antisense oligonucleotides that inhibited the expression of α11, β3, and γ5 subunits, as checked by immunocytochemistry. Intracellular dialysis of a carboxyl terminal anti-βcom antibody and a peptide corresponding to the Gβγ binding region of the β-adrenergic receptor kinase-1 had no effect on the ETAreceptor-mediated Ca2+ release. In contrast, a synthetic peptide corresponding to the carboxyl terminus of the αq/α11 subunit, heparin (an inhibitor of inositol 1,4,5-trisphosphate receptors), and U73122 (an inhibitor of phosphatidylinositol-phospholipase C) inhibited, in a concentration-dependent manner, the ETA receptor-mediated Ca2+ responses. Accumulation of [3H]inositol trisphosphate evoked by norepinephrine peaked at ∼15 s, whereas that evoked by ET-1 progressively increased within 2 min. In myocytes injected with anti-αq antisense oligonucleotides, both amplitude and time course of the norepinephrine-induced Ca2+ release became similar to those of the ET-1-induced Ca2+ response. We conclude that the ETAreceptor-mediated Ca2+ release is selectively transduced by the heterotrimeric G11 protein composed of α11, β3, and γ5 subunits, and that a delayed stimulation of phospholipase C occurs via the α11 subunit. The American Society for Pharmacology and Experimental Therapeutics