Suganuma A, Nakashima S, Okano Y, Nozawa Y
Department of Biochemistry, Gifu University School of Medicine, Japan.
Thromb Haemost. 1992 Sep 7;68(3):341-5.
Mass contents of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DG) were measured in U46619-stimulated human platelets. 1 microM of U46619 induced maximum responses in aggregation, 5-hydroxytryptamine (5HT) secretion and increase in intracellular free Ca2+ concentration ([Ca2+]i). Aggregation was almost comparable to that induced by maximal dose (1 U/ml) of thrombin, while 5HT release was almost half. The initial [Ca2+]i peak in response to U46619 was about half of thrombin stimulation. Production of IP3 and DG was, however, less than one tenth of that seen in thrombin stimulation. The profile (time course and concentration-dependency) of IP3 formation did not correlate with that of [Ca2+]i, suggesting that U46619 stimulates IP3-dependent and -independent Ca2+ mobilization. DG production was small but sustained for more than 5 min. These findings support the recent hypothesis that aggregation is regulated by a delayed accumulation of DG. The low level of 5HT secretion could be explained by the low production of second messengers, IP3 and DG.
在U46619刺激的人血小板中测量了肌醇1,4,5-三磷酸（IP3）和1,2-二酰甘油（DG）的大量含量。1微摩尔的U46619在聚集、5-羟色胺（5HT）分泌和细胞内游离Ca2+浓度（[Ca2+]i）增加方面诱导了最大反应。聚集几乎与最大剂量（1单位/毫升）凝血酶诱导的聚集相当，而5HT释放几乎是其一半。对U46619反应的初始[Ca2+]i峰值约为凝血酶刺激的一半。然而，IP3和DG的产生不到凝血酶刺激时的十分之一。IP3形成的曲线（时间进程和浓度依赖性）与[Ca2+]i的曲线不相关，表明U46619刺激IP3依赖性和非依赖性Ca2+动员。DG产生量小但持续超过5分钟。这些发现支持了最近的假说，即聚集受DG延迟积累的调节。5HT分泌水平低可以用第二信使IP3和DG产生量低来解释。
