HDL(3) ACTIVATES PHOSPHOLIPASE-D IN NORMAL BUT NOT IN GLYCOPROTEIN IIB/IIIA-DEFICIENT PLATELETS

Glycoprotein IIb/IIIa has been proposed as the platelet receptor for high density lipoproteins (HDL(3)). We characterized the HDL(3)-induced second messenger response in normal and glycoprotein IIb/IIIa-deficient platelets. In normal platelets physiological concentrations of HDL(3) induced the time-dependent generation of phosphatidic acid in the absence of phosphoinositide turnover. The rise in phosphatidic acid preceded that of diacyglycerol which was inconsistent with phospholipase C/diacylglycerol kinase pathway being the source of phosphatidic acid and suggested the involvement of phospholipase D. In the presence of butanol, HDL(3) stimulated the accumulation of phosphatidylbutanol, an unequivocal indicator of phospholipase D activity. No increase in phosphatidic acid, diacylglycerol, and phosphatidylbutanol was observed upon addition of HDL(3) to glycoprotein IIb/IIIa-deficient platelets. We conclude that phosphatidic acid is generated in HDL(3)-stimulated platelets by phospholipase D and that glycoprotein IIb/IIIa is the receptor involved in this process. (C) 1995 Academic Press, Inc.