Ikeda M, Onda T, Mitsubori T, Umegaki K, Tomita I, Tomita T
University of Shizuoka, Graduate School of Health Sciences, Japan.
J Pharmacobiodyn. 1992 Feb;15(2):49-57. doi: 10.1248/bpb1978.15.49.
Platelets from stroke-prone spontaneously hypertensive rats (SHRSP) show severe hypofunctions accompanied by defective protein (P47) phosphorylation. To examine the mechanism of platelet hypofunctions, phospholipid metabolism in SHRSP was compared with that in Wistar Kyoto rats (WKY). Phosphatidylinositol (PI) content was 20% less in SHRSP than in WKY, but no changes were observed in other phospholipids. Incorporation of [3H]-arachidonic acid (AA) into PI and phosphatidylethanolamine (PE) was 12% and 11% lower, and that into phosphatidylcholine (PC) was 6% higher in SHRSP than in WKY. Thrombin-induced diacylglycerol and phosphatidic acid formation were similar in both groups of platelets. Thrombin-induced release of [14C]-AA from the labeled platelets and its metabolism to eicosanoids occurred at similar rates. These results suggest that reduced formation of diacylglycerol, an activator of protein kinase C (PKC), does not cause defective phosphorylation of P47, a substrate of PKC, in SHRSP. However it remains unclear how the lower PI content and the altered distribution of AA in PC and PE is related to SHRSP platelet hypofunctions.
易患中风的自发性高血压大鼠（SHRSP）的血小板表现出严重的功能减退，并伴有蛋白质（P47）磷酸化缺陷。为了研究血小板功能减退的机制，将SHRSP的磷脂代谢与Wistar Kyoto大鼠（WKY）的进行了比较。SHRSP的磷脂酰肌醇（PI）含量比WKY低20%，但其他磷脂未观察到变化。与WKY相比，SHRSP中[3H]-花生四烯酸（AA）掺入PI和磷脂酰乙醇胺（PE）的量分别低12%和11%，而掺入磷脂酰胆碱（PC）的量高6%。两组血小板中凝血酶诱导的二酰基甘油和磷脂酸形成相似。凝血酶诱导的标记血小板中[14C]-AA释放及其代谢为类花生酸的速率相似。这些结果表明，蛋白激酶C（PKC）激活剂二酰基甘油形成减少并不会导致SHRSP中PKC底物P47的磷酸化缺陷。然而，尚不清楚较低的PI含量以及AA在PC和PE中分布的改变如何与SHRSP血小板功能减退相关。
