L-channel modulation by alpha-1 adrenoceptor activation in neonatal rat ventricular cells: intracellular mechanisms.
The alpha adrenergic agonist phenylephrine increases the long-lasting Ca++ channel current (L-type Ca++ channel current) in neonatal rat ventricular cells. In these experiments, the intracellular mechanism of the alpha (alpha-1A) adrenergic effect was investigated. Guanosine-5'-O-(2-thiodiphosphate), a G-protein inhibitor, blocked and guanosine-5'-O-(3-thiotriphosphate), a G-protein activator, mimicked the effect of phenylephrine, suggesting that G-proteins are involved in the activation of the alpha-1 adrenoceptor-induced increase in Ca++ channel current. The effect of phenylephrine on the L-type current was not abolished in cells pretreated with pertussis toxin and cholera toxin, indicating that pertussis toxin- and cholera toxin-insensitive G-proteins are coupled to the alpha-1A adrenoceptor. Acute treatment with 4 beta-phorbol-12-myristate and 1-oleoyl-2-acetyl-rac-glycerol, two protein kinase C activators, increased the L-type Ca++ channel current. Staurosporine and prolonged pretreatment with 4 beta-phorbol-12-myristate blocked the effect of phenylephrine. This suggests that protein kinase C activation is involved in the mechanism. The results described in this study suggest that stimulation of the alpha-1A adrenoceptor results in the activation of pertussis toxin- and cholera toxin-insensitive G-proteins which may lead to phosphorylation of Ca++ channel proteins through protein kinase C. The phosphorylation of channel protein results in an increase in the L-type Ca++ channel current in neonatal rat ventricular cells.
Department of Physiology, University of Alberta, Edmonton, Canada.
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Liu
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Karpinski
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D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D004075:Diglycerides; D018340:Receptors, Adrenergic, alpha-1; D010566:Virulence Factors, Bordetella; D010656:Phenylephrine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C038237:1-oleoyl-2-acetylglycerol; D002772:Cholera Toxin; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate