McGowan E B, Detwiler T C
Thromb Res. 1983 Jul 15;31(2):297-304. doi: 10.1016/0049-3848(83)90332-8.
Brief exposure of platelets to thrombin makes them less sensitive to subsequent activation by thrombin, a phenomenon demonstrated by Shuman, Botney, and Fenton [J. Clin. Invest., 63, 1211-1218, 1979] by incubating prostacyclin-inhibited platelets with thrombin; after removal of thrombin and prostacyclin, the platelets were selectively desensitized to subsequent activation by thrombin. The conditions for this desensitization have been further defined. Inhibition of thrombin-induced platelet activation by prostacyclin was not absolute, it was only temporary, it could be overcome with higher thrombin concentrations, and it varied with platelet concentration and temperature. With low enough thrombin concentrations, high enough prostacyclin concentrations and short enough times of exposure, platelets could be pretreated with thrombin with no evidence of activation. After addition of hirudin to inhibit thrombin, the platelets were washed and tested for thrombin-induced secretion of ATP. Desensitization to thrombin depended on the concentration of thrombin during pretreatment and on the length of pretreatment, consistent with a catalytic modification of a receptor. A less extensive desensitization was observed when platelets without inhibitor were incubated with a sub-threshold level of thrombin before addition of an activating concentration of thrombin. This desensitization also varied with the time of pretreatment and the concentration of sub-threshold thrombin.
血小板短暂暴露于凝血酶会使其对随后凝血酶的激活反应不那么敏感，这一现象由舒曼、博特尼和芬顿[《临床研究杂志》，63卷，1211 - 1218页，1979年]通过将前列环素抑制的血小板与凝血酶孵育得以证明；去除凝血酶和前列环素后，血小板对随后凝血酶的激活产生选择性脱敏。这种脱敏的条件已得到进一步明确。前列环素对凝血酶诱导的血小板激活的抑制并非绝对的，只是暂时的，可被更高浓度的凝血酶克服，并且随血小板浓度和温度而变化。在凝血酶浓度足够低、前列环素浓度足够高且暴露时间足够短的情况下，血小板可用凝血酶预处理而无激活迹象。加入水蛭素抑制凝血酶后，洗涤血小板并检测凝血酶诱导的ATP分泌。对凝血酶的脱敏取决于预处理期间凝血酶的浓度以及预处理的时长，这与受体的催化修饰一致。当在加入激活浓度的凝血酶之前，将未加抑制剂的血小板与亚阈值水平的凝血酶孵育时，观察到的脱敏程度较低。这种脱敏也随预处理时间和亚阈值凝血酶的浓度而变化。
