Modulation of Ca2+ channels by alpha 1A- and alpha 2A-adrenoceptors in vascular myocytes: involvement of different transduction pathways.
Using subtype-selective agonists and antagonists, and antibodies directed against phosphatidylinositol and G-proteins, it has been shown in single myocytes of rat portal vein that both alpha 1A- and alpha 2A-adrenoceptors modulate Ca2+ channels through two distinct transduction pathways. alpha 1A-adrenoceptors couple with a Gq/G11 protein to activate a phospholipase C (PLC) which hydrolyses phosphatidylinositol to generate inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 releases intracellular stored Ca2+ as evidenced by microspectrofluorimetry with Fura-2. The large and transient increase in [Ca2+]i activates chloride channels leading to a membrane depolarization that opens voltage-gated Ca2+ channels. In addition, DAG activates transiently protein kinase C (PKC) which increases the opening probability of Ca2+ channels through a phosphorylation-dependent process. alpha 2A-adrenoceptors do not induce Ca2+ release from intracellular stores but promote sustained Ca2+ influx through voltage-gated Ca2+ channels. The coupling involves a Gi-protein and activation of PKC by DAG. These two transduction pathways may be involved in the physiological action of noradrenaline in vascular smooth muscles.
Mironneau
J
J
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, URA CNRS 1489, Université de Bordeaux II, France.
Macrez-Leprêtre
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011169:Portal Vein; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium