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

J Biol Chem. 1997 Sep 12;272(37):23180-5. doi: 10.1074/jbc.272.37.23180.

Abstract

A G protein composed of alpha13, beta1, and gamma3 subunits selectively couples the angiotensin AT1A 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 Gbetagamma transduces the signal leading to stimulation of L-type Ca2+ channels. Intracellular dialysis through the patch pipette of a carboxyl-terminal anti-betacom antibody and a peptide corresponding to the Gbetagamma binding region of the beta-adrenergic receptor kinase 1 inhibited the stimulation of Ca2+ channels and the increase in [Ca2+]i evoked by angiotensin II. The Gbetagamma 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 Galphaq in response to stimulation of alpha1-adrenoreceptors. Transient overexpression of the beta-adrenergic receptor kinase 1 fragment and of Galpha subunits also inhibited the angiotensin II-induced increase in [Ca2+]i. Both anti-alpha13 antibody and carboxyl-terminal alpha13 peptide abrogated the angiotensin II-induced stimulation of Ca2+ channels. We conclude that activation of angiotensin AT1 receptors requires all three alpha, beta, and gamma subunits of G13 for receptor-G protein interaction, whereas the transduction of the signal to L-type Ca2+ channels is mediated by Gbetagamma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiotensin II / pharmacology
  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type
  • Cell Separation
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dimerization
  • Electric Conductivity
  • Enzyme Activation
  • GTP-Binding Proteins / metabolism*
  • Molecular Sequence Data
  • Muscle Proteins / metabolism
  • Muscle, Smooth, Vascular / metabolism*
  • Portal Vein / cytology
  • Portal Vein / metabolism*
  • Rats
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Angiotensin / metabolism*
  • Signal Transduction
  • Type C Phospholipases / metabolism
  • beta-Adrenergic Receptor Kinases

Substances

  • Calcium Channels
  • Calcium Channels, L-Type
  • Muscle Proteins
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Adrenergic, alpha-1
  • Receptors, Angiotensin
  • Angiotensin II
  • Cyclic AMP-Dependent Protein Kinases
  • beta-Adrenergic Receptor Kinases
  • Type C Phospholipases
  • GTP-Binding Proteins
  • Calcium