A βγ dimer derived from G13 transduces the angiotensin AT1 receptor signal to stimulation of Ca2+ channels in rat portal vein myocytes

Abstract

A G protein composed of α13, β1, and γ3 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 Gβγ transduces the signal leading to stimulation of L-type Ca2+ channels. Intracellular dialysis through the patch pipette of a carboxyl-terminal anti-β(com) antibody and a peptide corresponding to the Gβγ binding region of the β-adrenergic receptor kinase 1 inhibited the stimulation of Ca2+ channels and the increase in [Ca2+](i) evoked by angiotensin II. The Gβγ, binding peptide did not prevent the dissociation of the heterotrimeric G protein into its subunits, as it did not block activation of phospholipase C-β by Gα(q) in response to stimulation of α1-adrenoreceptors. Transient overexpression of the β-adrenergic receptor kinase 1 fragment and of Gα subunits also inhibited the angiotensin II-induced increase in [Ca2+](i). Both anti- α13 antibody and carboxyl-terminal α13 peptide abrogated the angiotensin II-induced stimulation of Ca2+ channels. We conclude that activation of angiotensin AT1 receptors requires all three α, β, and γ subunits of G13 for receptor-G protein interaction, whereas the transduction of the signal to L-type Ca2+ channels is mediated by Gβγ.