A beta gamma dimer derived from G(13) transduces the angiotensin AT(1) receptor signal to stimulation of Ca2+ channels in rat portal vein myocytes

A G protein composed of alpha(13), beta(1) and gamma(3) subunits selectively couples the angiotensin AT(1A) receptors to increase cytoplasmic Ca2+ concentration ([Ca2+](i)) in rat portal vein myocytes (Macrez-Lepretre, N., Kalkbrenner, F., Morel, J. L., Schultz, G., and Mironneau, J. (1997) J. Biol. Chem. 272, 10095-10102). We show here that G beta gamma transduces the signal leading to stimulation of L-type Ca2+ channels, Intracellular dialysis through the patch pipette of a carboxyl-terminal anti-beta(com) antibody and a peptide corresponding to the G beta gamma binding region of She beta-adrenergic receptor kinase 1 inhibited the stimulation of Ca2+ channels and the increase in [Ca2+](i) evoked by angiotensin II. The G beta gamma binding peptide did not prevent the dissociation of the heterotrimeric G protein into its subunits, as it did not block activation of phospholipase C-beta by G alpha(q) in response to stimulation of alpha(1)-adrenoreceptors. Transient overexpression of the beta-adrenergic receptor kinase 1 fragment and of G alpha subunits also inhibited the angiotensin II-induced increase in [Ca2+](i). Both anti-alpha(13) antibody and carboxyl-terminal alpha(13) peptide abrogated the angiotensin II-induced stimulation of Ca2+ channels, We conclude that activation of angiotensin AT(1) receptors requires all three alpha, beta, and gamma subunits of G(13) for receptor-G protein interaction, whereas the transduction of the signal to L-type Ca2+ channels is mediated by G beta gamma.