Involvement of both G protein alphas and beta gamma subunits in beta-adrenergic stimulation of vascular L-type Ca(2+) channels.
British Journal of Pharmacology. 2001-02-01; 132(3): 669-676
DOI: 10.1038/sj.bjp.0703864
Lire sur PubMed
1. Br J Pharmacol. 2001 Feb;132(3):669-76.
Involvement of both G protein alphas and beta gamma subunits in beta-adrenergic
stimulation of vascular L-type Ca(2+) channels.
Viard P(1), Macrez N, Mironneau C, Mironneau J.
Author information:
(1)Laboratoire de Signalisation et Interactions Cellulaires, CNRS UMR 5017,
Université de Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
1. Previous data have shown that activation of beta(3)-adrenoceptors stimulates
vascular L-type Ca(2+) channels through a G alphas-induced stimulation of the
cyclic AMP/PKA pathway. The present study investigated whether beta-adrenergic
stimulation also uses the G beta gamma/PI3K/PKC pathway to modulate L-type Ca(2+)
channels in rat portal vein myocytes. 2. Peak Ba(2+) current (I(Ba)) measured
using the whole-cell patch clamp method was maximally increased by application of
10 microm isoprenaline after blockade of beta(3)-adrenoceptors by 1 microM
SR59230A. Under these conditions, the isoprenaline-induced stimulation of I(Ba)
was reversed by ICI-118551 (a specific beta(2)-adrenoceptor antagonist) but not
by atenolol (a specific beta(1)-adrenoceptor antagonist). The
beta(2)-adrenoceptor agonist salbutamol increased I(Ba), an effect which was
reversed by ICI-118551 whereas the beta(1)-adrenoceptor agonist dobutamine had no
effect on I(Ba). 3. Application of PKA inhibitors (H-89 and Rp 8-Br-cyclic AMPs)
or a PKC inhibitor (calphostin C) alone did not affect the beta(2)-adrenergic
stimulation of I(Ba) whereas simultaneous application of both PKA and PKC
inhibitors completely blocked this stimulation. 4. The beta(2)-adrenergic
stimulation of L-type Ca(2+) channels was blocked by a pre-treatment with cholera
toxin and by intracellular application of an anti-G alphas antibody (directed
against the carboxyl terminus of G alphas). In the presence of H-89,
intracellular infusion of an anti-Gss(com) antibody or a beta ARK(1) peptide as
well as a pre-treatment with wortmannin (a PI3K inhibitor) blocked the
beta(2)-adrenergic stimulation of I(Ba). 5. These results suggest that the
beta(2)-adrenergic stimulation of vascular L-type Ca(2+) channels involves both G
alphas and G beta gamma subunits which exert their stimulatory effects through
PKA and PI3K/PKC pathways, respectively.
DOI: 10.1038/sj.bjp.0703864
PMCID: PMC1572606
PMID: 11159719 [Indexed for MEDLINE]