Abstract
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.
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