Stimulation and binding of myocardial phospholipase c by
phosphatidic acid.
Henry, Ross A., Sharon Y. Boyce, Thomas Kurz, and Robert A. Wolf.
Cardiovascular Division, Department of Internal Medicine,
Washington University School of Medicine, St. Louis, Missouri USA
APStracts 2:0085C, 1995.
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, in concentrations of 10-8 M to 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 EGTA. PLC-[delta]1, the predominant isoenzyme 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 both in vitro stimulation of myocytic PLC activity
and to 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.
Received 19 January 1995; accepted in final form 24 January 1995.
APS Manuscript Number C38-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 February 1995.