BIOCHEMICAL-CHARACTERIZATION OF THE INTERACTION OF LIPID PHOSPHORIC-ACIDS WITH HUMAN PLATELETS - COMPARISON WITH PLATELET-ACTIVATING-FACTOR

A series of lipid phosphoric acids, including 1-O-alkyl-2-lyso-glycero phosphoric acid, 1-O-acyl-2-lyso-glycerophosphoric acid, hexadecylprop anediolphosphoric acid, N-acyl-2-aminoethanolphosphoric acid, sphingos ine phosphoric acid, and certain homologues and analogues, were synthe sized and characterized by thin-layer chromatography, fast-atom bombar dment mass spectrometry, and their ability to aggregate human platelet s. The presence of a receptor for these lipid phosphoric acids that is distinct from the PAF receptor is strongly suggested from experiments involving a desensitization procedure, platelet-activating factor (PA F) receptor antagonists, and inhibitors of the lipid phosphoric acids. The unique features of the interaction of these lipid phosphoric acid s with platelets include: (a) evidence for a separate receptor(s) for this diverse group of synthetic compounds, (b) no requirement for ster eospecificity (i.e., no glycerol backbone), and (c) a structural requi rement for a long-chain hydrocarbon residue covalently bound to a phos phoric acid residue. In the interaction of these compounds with the pl atelet, it is mandatory that extracellular Ca2+ and ADP be present for maximum biological activity. The potential involvement of a lipid pho sphoric acid receptor, which could form a component of the activation pathway associated with various lysophospholipids and analogues, such as PAF, via a phospholipase D activation, is discussed.(C) 1994 Academ ic Press, Inc.