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Volume 272, Number 37, Issue of September 12, 1997 pp. 23180-23185
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

A Dimer Derived from G₁₃ Transduces the Angiotensin AT₁ Receptor Signal to Stimulation of Ca²⁺ Channels in Rat Portal Vein Myocytes

(Received for publication, April 25, 1997)

Nathalie Macrez , Jean-Luc Morel , Frank Kalkbrenner ^¶ , Patricia Viard , Günter Schultz ^¶ and Jean Mironneau

From the  Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, CNRS ESA 5017, Université de Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France and ^¶ Institut für Pharmakologie, Freie Universität Berlin, Thielallee 69/73, D-14195 Berlin, Germany

A G protein composed of ₁₃, ₁, and ₃ subunits selectively couples the angiotensin AT_1A receptors to increase cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) in rat portal vein myocytes (Macrez-Leprêtre, N., Kalkbrenner, F., Morel, J. L., Schultz, G., and Mironneau, J. (1997) J. Biol. Chem. 272, 10095-10102). We show here that G transduces the signal leading to stimulation of L-type Ca²⁺ channels. Intracellular dialysis through the patch pipette of a carboxyl-terminal anti-_com antibody and a peptide corresponding to the G binding region of the -adrenergic receptor kinase 1 inhibited the stimulation of Ca²⁺ channels and the increase in [Ca²⁺]_i evoked by angiotensin II. The G binding peptide did not prevent the dissociation of the heterotrimeric G protein into its subunits, as it did not block activation of phospholipase C- by G_q in response to stimulation of ₁-adrenoreceptors. Transient overexpression of the -adrenergic receptor kinase 1 fragment and of G subunits also inhibited the angiotensin II-induced increase in [Ca²⁺]_i. Both anti-₁₃ antibody and carboxyl-terminal ₁₃ peptide abrogated the angiotensin II-induced stimulation of Ca²⁺ channels. We conclude that activation of angiotensin AT₁ receptors requires all three , , and  subunits of G₁₃ for receptor-G protein interaction, whereas the transduction of the signal to L-type Ca²⁺ channels is mediated by G.

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