Thrombin-induced inositol trisphosphate production by rabbit platelets is inhibited by ethanol.
Thrombin-induced inositol trisphosphate production by rabbit platelets is inhibited by ethanol.
复制标题
乙醇抑制兔血小板凝血酶诱导的肌醇三磷酸的产生。
作者：
M. Rand;J. Vickers;R. Kinlough;M. Packham;J. Mustard
乙醇对某些血小板功能有抑制作用，但其作用机制尚不清楚。用洗涤过的血小板悬液，我们观察到乙醇(1-9 mg/ml)不影响ADP(0.5-10微米)刺激的兔血小板聚集。当用5-羟基[14C]色胺预先标记血小板时，乙醇不能抑制凝血酶(0.01-0.10单位/毫升)对颗粒内容物的聚集和分泌，但对较低浓度(<0.01单位/毫升)的凝血酶的这种反应可被乙醇(2-4 mg/毫升)抑制。用[~3H]肌醇预先标记血小板，这样就可以通过测量这些化合物中的标记量来评估刺激时肌醇磷酸盐的增加。乙醇不影响ADP引起的IP(肌醇磷酸)和IP2(肌醇二磷酸)升高。ADP和乙醇对IP3(三磷酸肌醇)无影响。尽管乙醇不影响凝血酶浓度大于0.01单位/毫升时引起的IP、IP2和IP3的升高，但乙醇能抑制较低浓度凝血酶(<0.01单位/毫升)刺激2分钟和3分钟后这些肌醇磷酸酶的升高。由于ADP不会引起兔血小板IP3的形成，而且在较低浓度的凝血酶刺激下的血小板中没有检测到血栓烷B2，因此乙醇抑制IP3的形成不太可能是由于释放的ADP或血栓素A2对血小板的进一步刺激所致。乙醇可能通过抑制第二信使IP3的产生来抑制血小板对凝血酶的反应。
Ethanol has an inhibitory effect on some platelet functions, but the mechanisms by which it exerts this effect are not known. Using suspensions of washed platelets, we observed that ethanol (1-9 mg/ml) did not affect the aggregation of rabbit platelets stimulated with ADP (0.5-10 microM). When platelets were prelabelled with 5-hydroxy[14C]tryptamine, aggregation and secretion of granule contents in response to thrombin (0.01-0.10 unit/ml) were not inhibited by ethanol, but these responses to thrombin at lower concentrations (less than 0.01 unit/ml) were inhibited by ethanol (2-4 mg/ml). Platelets were prelabelled with [3H]inositol so that increases in inositol phosphates upon stimulation could be assessed by measuring the amount of label in these compounds. ADP-induced increases in IP (inositol phosphate) and IP2 (inositol bisphosphate) were not affected by ethanol. IP3 (inositol trisphosphate) was not changed by ADP or ethanol. Although ethanol did not affect the increases in IP, IP2 and IP3 caused by stimulation of platelets with thrombin at concentrations greater than 0.01 unit/ml, ethanol did inhibit the increases observed at 2 and 3 min in these inositol phosphates caused by lower concentrations of thrombin (less than 0.01 unit/ml). Since ADP did not cause formation of IP3 in rabbit platelets, and since no thromboxane B2 was detected in platelets stimulated with the lower concentrations of thrombin, it is unlikely that the inhibitory effect of ethanol in IP3 formation was due to effects on further stimulation of platelets by released ADP or by thromboxane A2. Ethanol may inhibit platelet responses to thrombin by inhibiting the production of the second messenger, IP3.