STIMULATION AND BINDING OF MYOCARDIAL PHOSPHOLIPASE-C BY PHOSPHATIDIC-ACID

Exposure of adult ventricular myocytes to exogenous natural phosphatid ic acid results in the production of inositol phosphates by unknown me chanism(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 pr oduction. Our data demonstrate that exogenous PA, at 10(-8)-10(-5) M, caused a concentration-dependent increase in inositol 1,4,5-trisphosph ate in adult rabbit ventricular myocytes. PA also caused a concentrati on-dependent increase in in vitro activity of myocytic PLC in the pres ence or absence of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N '-tetraacetic acid (EGTA). PLC-delta(1), the predominant isozyme of PL C expressed in adult rabbit ventricular myocytes, bound to liposomes o f PA with high affinity in the presence of EGTA. The phosphomonoester group of PA was critical to in vitro stimulation of myocytic PLC activ ity 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 dyn amic membrane association and modulation of PLC in adult ventricular m yocytes.