Torti M, Tolnai Festetics E, Bertoni A, Sinigaglia F, Balduini C
Department of Biochemistry, University of Pavia, Italy.
FEBS Lett. 1998 Jul 10;431(1):19-22. doi: 10.1016/s0014-5793(98)00712-1.
Stimulation of human platelets with thrombin caused a 42% inhibition of the ADP-ribosyl cyclase activity of membrane CD38. This effect was mediated by the activation of the platelet thrombin receptor rather than by proteolysis of CD38, and was not due to a different distribution of the synthesised nucleotide or to a reduced accessibility of CD38 to the substrate. The inhibitory effect of thrombin required actin polymerisation and was not observed when interaction of CD38 with the cytoskeleton was prevented by cytochalasin D. Finally, we analysed whether cADPR could play a role as a Ca2+-mobilising agent in human platelets. Using saponin-permeabilised cells, we found that unlike IP3, cADPR did not induce any release of Ca2+ from intracellular stores. These results indicate that the enzymatic activity of membrane CD38 can be modulated by platelet activation, and that the function of this glycoprotein is probably not related to Ca2+ mobilisation.
用凝血酶刺激人血小板会导致膜CD38的ADP - 核糖基环化酶活性受到42%的抑制。这种效应是由血小板凝血酶受体的激活介导的，而非CD38的蛋白水解作用，并且不是由于合成核苷酸的不同分布或CD38对底物的可及性降低所致。凝血酶的抑制作用需要肌动蛋白聚合，当用细胞松弛素D阻止CD38与细胞骨架的相互作用时，未观察到这种抑制作用。最后，我们分析了环ADP核糖（cADPR）是否能在人血小板中作为一种钙动员剂发挥作用。使用皂素通透细胞，我们发现与肌醇三磷酸（IP3）不同，cADPR不会诱导细胞内钙库释放任何钙离子。这些结果表明，膜CD38的酶活性可被血小板激活所调节，并且这种糖蛋白的功能可能与钙动员无关。
