Exogenous cholesterol--initiated transmembrane signalling pathway regulates cholesterogenesis in human platelets

Incubation of gel-filtered human platelets with cholesterol in the absence of divalent ions revealed that exogenous cholesterol had the ability to down-regulate the cholesterol biosynthesis in a dose-dependent fashion and this phenomenon was paralleled by an increase in phospholipase D activity. However, exogenous calcium in the presence of either cholesterol or phosphatidic acid had the capacity to up-regulate the platelet cholesterol synthesis in a dose-dependent manner. Further, cyclic nucleotides (cAMP, cGMP) also had the ability to influence directly the regulation of platelet cholesterol synthesis. Based upon these, as well as our earlier findings, we propose that exogenous cholesterol through its specific receptor regulates cholesterogenesis either directly or by initiating the transmembrane-signalling pathway involving cyclic nucleotides.