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-glycerophosphoric acid, 1-O-acyl-2-lyso-glycerophosphoric acid, hexadecylpropanediolphosphoric acid, N-acyl-2-aminoethanolphosphoric acid, sphingosine phosphoric acid, and certain homologues and analogues, were synthesized and characterized by thin-layer chromatography, fast-atom bombardment mass spectrometry, and their ability to aggregate human platelets. 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 (PAF) receptor antagonists, and inhibitors of the lipid phosphoric acids. The unique features of the interaction of these lipid phosphoric acids with platelets include: (a) evidence for a separate receptor(s) for this diverse group of synthetic compounds, (b) no requirement for stereospecificity (i.e., no glycerol backbone), and (c) a structural requirement for a long-chain hydrocarbon residue covalently bound to a phosphoric acid residue. In the interaction of these compounds with the platelet, it is mandatory that extracellular Ca2+ and ADP be present for maximum biological activity. The potential involvement of a lipid phosphoric 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.
Sugiura
T
T
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Tokumura
A
A
Gregory
L
L
Nouchi
T
T
Weintraub
S T
ST
Hanahan
D J
DJ
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D015394:Molecular Structure; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010743:Phospholipids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface