Biochemical Characterization of the Interaction of Lipid Phosphoric Acids with Human Platelets: Comparison with Platelet Activating Factor

• Published in: Archives of biochemistry and biophysics Vol. 311; no. 2; pp. 358 - 368
• Main Authors: Sugiura, T., Tokumura, A., Gregory, L., Nouchi, T., Weintraub, S.T., Hanahan, D.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.1994
• Subjects: Blood Platelets - drug effects; Blood Platelets - metabolism; Humans; In Vitro Techniques; Indicators and Reagents; Molecular Structure; Phosphatidylethanolamines - chemistry; Phospholipids - chemical synthesis; Phospholipids - chemistry; Phospholipids - pharmacology; Platelet Activating Factor - pharmacology; Platelet Aggregation - drug effects; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - metabolism; Spectrometry, Mass, Fast Atom Bombardment; Structure-Activity Relationship
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1006/abbi.1994.1249

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.