Involvement of both G protein αs and βγ subunits in β-adrenergic stimulation of vascular L-type Ca2+ channels

SR59230A. Under these conditions, the isoprenaline-induced stimulation of IBa was reversed by ICI-118551 (a specific b2-adrenoceptor antagonist) but not by atenolol (a specific b1-adrenoceptor antagonist). The b2-adrenoceptor agonist salbutamol increased IBa, an eAect which was reversed by ICI-118551 whereas the b1-adrenoceptor agonist dobutamine had no eAect on IBa. 3 Application of PKA inhibitors (H-89 and Rp 8-Br-cyclic AMPs) or a PKC inhibitor (calphostin C) alone did not aAect the b2-adrenergic stimulation of IBa whereas simultaneous application of both PKA and PKC inhibitors completely blocked this stimulation. 4 The b2-adrenergic stimulation of L-type Ca 2+ channels was blocked by a pre-treatment with cholera toxin and by intracellular application of an anti-Gas antibody (directed against the carboxyl terminus of Gas). In the presence of H-89, intracellular infusion of an anti-Gbcom antibody or a bARK1 peptide as well as a pre-treatment with wortmannin (a PI3K inhibitor) blocked the b2adrenergic stimulation of IBa. 5 These results suggest that the b2-adrenergic stimulation of vascular L-type Ca 2+ channels involves both Gas and Gbg subunits which exert their stimulatory eAects through PKA and PI3K/ PKC pathways, respectively. British Journal of Pharmacology (2001) 132, 669‐676