Sugiura T, Tokumura A, Gregory L, Nouchi T, Weintraub S T, Hanahan D J
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Arch Biochem Biophys. 1994 Jun;311(2):358-68. 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.
合成了一系列脂磷酸，包括1-O-烷基-2-溶血甘油磷酸、1-O-酰基-2-溶血甘油磷酸、十六烷基丙二醇磷酸、N-酰基-2-氨基乙醇磷酸、鞘氨醇磷酸以及某些同系物和类似物，并通过薄层色谱、快原子轰击质谱以及它们聚集人血小板的能力对其进行了表征。涉及脱敏程序、血小板活化因子（PAF）受体拮抗剂和脂磷酸抑制剂的实验强烈表明，存在一种与PAF受体不同的这些脂磷酸的受体。这些脂磷酸与血小板相互作用的独特特征包括：（a）有证据表明存在针对这一多样的合成化合物组的单独受体；（b）不需要立体特异性（即不需要甘油主链）；（c）对与磷酸残基共价结合的长链烃残基有结构要求。在这些化合物与血小板的相互作用中，细胞外Ca2+和ADP的存在对于最大生物活性是必不可少的。本文讨论了脂磷酸受体的潜在参与，该受体可能通过磷脂酶D激活形成与各种溶血磷脂和类似物（如PAF）相关的激活途径的一个组成部分。
