Modification of intracellular free calcium in cultured A10 vascular smooth muscle cells by exogenous phosphatidic acid.
Exogenous phosphatidic acid (PA) was observed to produce a concentration-dependent increase in [Ca(2+)](i) in cultured A10 vascular smooth muscle cells. Preincubation of cells with sarcoplasmic reticulum Ca(2+)-ATPase inhibitors (cyclopiazonic acid and thapsigargin), a phospholipase C inhibitor (2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate), inositol 1,4,5-trisphosphate receptor antagonists (2-aminoethoxydiphenyl borate and xestospongin), and an activator of protein kinase C (PKC) (phorbol 12-myristate 13-acetate) depressed the PA-evoked increase in [Ca(2+)](i). Although EGTA, an extracellular Ca(2+) chelator, decreased the PA-induced increase in [Ca(2+)](i), sarcolemmal Ca(2+)-channel blockers (verapamil or diltiazem) did not alter the action of PA. On the other hand, inhibitors of PKC (bisindolylmaleimide I) and G(i)-protein (pertussis toxin) potentiated the increase in [Ca(2+)](i) evoked by PA significantly. These results suggest that the PA-induced increase in [Ca(2+)](i) in vascular smooth muscle cells may occur upon the activation of phospholipase C and the subsequent release of Ca(2+) from the inositol 1,4,5-trisphosphate-sensitive Ca(2+) pool in the sarcoplasmic reticulum. This action of PA may be mediated through the involvement of PKC.
Bhugra
Praveen
P
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, Man., Canada R2H 2A6.
Xu
Yan-Jun
YJ
Rathi
Satyajeet
S
Dhalla
Naranjan S
NS
D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002219:Carbamates / Q000494:pharmacology; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D047028:Macrocyclic Compounds; D008301:Maleimides / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010080:Oxazoles / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D048448:Phenylcarbamates; D010712:Phosphatidic Acids / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D001896:Boron Compounds; D002219:Carbamates; D007211:Indoles; D047028:Macrocyclic Compounds; D008301:Maleimides; D010080:Oxazoles; D048448:Phenylcarbamates; D010712:Phosphatidic Acids; C108644:xestospongin A; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; D004533:Egtazic Acid; D019284:Thapsigargin; D014700:Verapamil; C109986:2-aminoethoxydiphenyl borate; D037342:Pertussis Toxin; D004110:Diltiazem; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; C000543:cyclopiazonic acid