Angiotensin II-mediated activation of L-type calcium channels involves phosphatidylinositol hydrolysis-independent activation of protein kinase C in rat portal vein myocytes.
The action of angiotensin II (ANG II) was studied in single myocytes from rat portal vein, in which the cytoplasmic Ca++ concentration was estimated by emission from fluorescent dyes and the Ca++ channel current was measured with the whole-cell mode of the patch-clamp technique. ANG II stimulated Ca++ channel current through L-type Ca++ channels and initiated a slow and small increase in the cytoplasmic Ca++ concentration in cells in which intracellular Ca++ stores had been depleted by pretreatment with ryanodine and caffeine. Both Ca++ channel current stimulation and Ca++ responses were selectively inhibited by losartan, indicating activation of angiotensin AT1 receptors. Activation of Ca++ channels by ANG II was insensitive to treatment with pertussis toxin and cholera toxin. Intracellular applications of anti-G alpha q/alpha 11 and anti-phosphatidylinositol antibodies had no effect on the ANG II-induced stimulation of Ca++ channel current, indicating that phosphatidylinositol-specific phospholipase C was not involved in this signaling pathway. Down-regulation of protein kinase C and application of an inhibitor of protein kinase C blocked the ANG II-induced effects. Tricyclodecan-9-yl xanthogenate (an inhibitor of non-phosphatidylinositol-specific phospholipases C and phospholipases D) but not propranolol (an inhibitor of phospholipase D-derived diacylglycerol formation) suppressed the ANG II-induced effects. These data suggest that phosphatidylcholine-specific phospholipase C is involved in the ANG II signaling pathway leading to stimulation of L-type Ca++ channels by protein kinase C.
Macrez-Leprêtre
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N
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, CNRS ESA 5017, Université de Bordeaux II, Faculté de Pharmacie, France.
Morel
J L
JL
Mironneau
J
J
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis / Q000187:drug effects; D010716:Phosphatidylinositols / Q000378:metabolism; D011169:Portal Vein / Q000187:drug effects*; D011493:Protein Kinase C / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D010716:Phosphatidylinositols; D000804:Angiotensin II; D011493:Protein Kinase C