Stimulation and binding of myocardial phospholipase C by phosphatidic acid.
Exposure of adult ventricular myocytes to exogenous natural phosphatidic acid results in the production of inositol phosphates by unknown mechanism(s). We characterized stimulation of myocytic phosphoinositide-specific phospholipase C (PLC) by synthetic dioleoyl phosphatidic acid (PA) as a potential mechanism for modulation of inositol phosphate production. Our data demonstrate that exogenous PA, at 10(-8)-10(-5) M, caused a concentration-dependent increase in inositol 1,4,5-trisphosphate in adult rabbit ventricular myocytes. PA also caused a concentration-dependent increase in in vitro activity of myocytic PLC in the presence or absence of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). PLC-delta 1, the predominant isozyme of PLC expressed in adult rabbit ventricular myocytes, bound to liposomes of PA with high affinity in the presence of EGTA. The phosphomonoester group of PA was critical to in vitro stimulation of myocytic PLC activity and high-affinity binding of PLC-delta 1. We propose that binding of PLC-delta 1 to phosphatidic acid may be a novel mechanism for dynamic membrane association and modulation of PLC in adult ventricular myocytes.
Henry
R A
RA
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Boyce
S Y
SY
Kurz
T
T
Wolf
R A
RA
D000818:Animals; D002417:Cattle; D002850:Chromatography, Gel; D004351:Drug Resistance; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D008055:Lipids / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010715:Phosphatidylglycerols / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D011817:Rabbits; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D008055:Lipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases