Isolation of a phospholipid inhibitor of platelet activating factor-induced activity from perfused rat liver: identification as phosphatidylglycerol.
Isolation of a phospholipid inhibitor of platelet activating factor-induced activity from perfused rat liver: identification as phosphatidylglycerol.
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从灌注的大鼠肝脏中分离血小板激活因子诱导的活性的磷脂抑制剂：鉴定为磷脂酰甘油。
DOI：
10.1006/abbi.1993.1227
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发表时间：
1993
影响因子：
3.9
通讯作者：
Hanahan,DJ
中科院分区：
文献类型：
--
作者：
Lekka,M;Tokumura,A;Tsuji,H;Hanahan,DJ
从灌注的大鼠肝脏中分离出血小板激活因子作用的内源性抑制剂。通过薄层色谱和高效液相色谱对其进行纯化，并进行化学修饰以鉴定其结构。根据其快原子轰击质谱，其特征为磷脂酰甘油，主要由 16:0/18:1 和 16:0/20:2 脂肪酰基链（分别为 [M + H]+atm/z749 和 775）以及极少量的 18:0/18:1 和 18:0/20:2 组成。纯化的化合物对 5 × 10−10M 血小板激活因子 (PAF) 诱导的兔血小板聚集具有抑制作用，EC50 值接近 2.5 × 10−6M，对血清素分泌的抑制作用为 EC507 × 10−6M。从肝脏制备物中分离出的其他磷脂，例如磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰肌醇、鞘磷脂、心磷脂（二磷脂酰甘油）和磷脂酸，在 1 × 10−4 至 1 × 10−7M 的浓度范围内没有表现出抑制活性，也不会诱导血小板的任何聚集或裂解。重要的是，磷脂酰甘油可以抑制凝血酶和 ADP 诱导的兔血小板聚集。这些结果表明这些激动剂的信号转导途径可能存在共同的抑制位点。初步结合实验表明 PAF 与完整兔血小板的结合具有非竞争性抑制作用。
An endogenous inhibitor of platelet activating factor action was isolated from perfused rat liver. It was purified by thin-layer chromatography and high-performance liquid chromatography and subjected to chemical modifications in order to identify its structure. On the basis of its fast atom bombardment-mass spectrum it was characterized as phosphatidylglycerol composed mainly of 16:0/18:1 and 16:0/20:2 fatty acyl chains ([M + H]+atm/z749 and 775, respectively) and very minor levels of 18:0/18:1 and 18:0/20:2. The purified compound exhibited inhibition on rabbit platelet aggregation induced by 5 × 10−10M platelet activating factor (PAF) at an EC50value near 2.5 × 10−6M and on the serotonin secretion at an EC507 × 10−6M. Other phospholipids isolated from the liver preparations, such as phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, cardiolipin (diphosphatidylglycerol), and phosphatidic acid, exhibited no inhibitory activity in the concentration range from 1 × 10−4to 1 × 10−7M nor did they induce any aggregation, or lysis, of the platelets. Of importance, phosphatidylglycerol could inhibit thrombin- and ADP-induced aggregation of rabbit platelets. These results suggested a possible site of inhibition common to the signal transduction pathway of these agonists. Preliminary binding experiments showed a noncompetitive type of inhibition on PAF binding to intact rabbit platelets.