Beta-3 adrenergic stimulation of L-type Ca(2+) channels in rat portal vein myocytes.

Patricia Viard, Nathalie Macrez, Frédéric Coussin, Jean-Luc Morel, Jean Mironneau
British Journal of Pharmacology. 2000-04-01; 129(7): 1497-1505
DOI: 10.1038/sj.bjp.0703187

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1. Br J Pharmacol. 2000 Apr;129(7):1497-505.

Beta-3 adrenergic stimulation of L-type Ca(2+) channels in rat portal vein
myocytes.

Viard P(1), Macrez N, Coussin F, Morel JL, Mironneau J.

Author information:
(1)Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, CNRS UMR
5017, Université de Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux Cedex,
France.

1. The effects of beta(3)-adrenergic stimulation were studied on the L-type
Ca(2+) channel in single myocytes from rat portal vein using the whole-cell mode
of the patch-clamp technique. 2. Reverse transcription-polymerase chain reaction
showed that beta(1)-, beta(2)- and beta(3)-adrenoceptor subtypes were expressed
in rat portal vein myocytes. Application of both propranolol (a non-selective
beta(1)- and beta(2)-adrenoceptor antagonist) and SR59230A (a
beta(3)-adrenoceptor antagonist) were needed to inhibit the isoprenaline-induced
increase in L-type Ca(2+) channel current. 3. L-type Ca(2+) channels were
stimulated by CGP12177A (a beta(3)-adrenoceptor agonist with potent beta(1)- and
beta(2)-adrenoceptor antagonist property) in a manner similar to that of
isoprenaline. The CGP12177A-induced stimulation of Ca(2+) channel current was
blocked by SR59230A, cyclic AMP-dependent protein kinase inhibitors, H-89 and Rp
8-Br-cyclic AMPs, but was unaffected by protein kinase C inhibitors, GF109203X
and 19-31 peptide. This stimulation was mimicked by forskolin and 8-Br-cyclic
AMP. In the presence of okadaic acid (a phosphatase inhibitor), the
beta(3)-adrenoceptor-induced stimulation was maintained after withdrawal of the
agonist. 4. The beta(3)-adrenoceptor stimulation of L-type Ca(2+) channels was
blocked by a pretreatment with cholera toxin and by the intracellular application
of an anti-Galpha(s) antibody. This stimulation was unaffected by intracellular
infusion of an anti-Gbeta(com) antibody and a betaARK(1) peptide. 5. These
results show that activation of beta(3)-adrenoceptors stimulates L-type Ca(2+)
channels in vascular myocytes through a Galpha(s)-induced stimulation of the
cyclic AMP/protein kinase A pathway and the subsequent phosphorylation of the
channels.

DOI: 10.1038/sj.bjp.0703187
PMCID: PMC1571970
PMID: 10742307 [Indexed for MEDLINE]

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