Radomski M W, Palmer R M, Moncada S
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Proc Natl Acad Sci U S A. 1990 Jul;87(13):5193-7. doi: 10.1073/pnas.87.13.5193.
Aggregation of human washed platelets with collagen is accompanied by a concentration-dependent increase in cyclic GMP but not cyclic AMP. NG-Monomethyl-L-arginine (L-MeArg), a selective inhibitor of nitric oxide (NO) synthesis from L-arginine, reduces this increase and enhances aggregation. L-Arginine, which has no effect on the basal levels of cyclic GMP, augments the increase in this nucleotide induced by collagen and also inhibits aggregation. Both of these effects of L-arginine are attenuated by L-MeArg. The anti-aggregatory action of L-arginine is potentiated by prostacyclin and by M&B22948, a selective inhibitor of the cyclic GMP phosphodiesterase, but not by HL725, a selective inhibitor of the cyclic AMP phosphodiesterase. L-Arginine also inhibits platelet aggregation in whole blood in a similar manner, although the concentrations required are considerably higher. L-Arginine stimulates the soluble guanylate cyclase and increases cyclic GMP in platelet cytosol. This stimulation is dependent on NADPH and Ca2+ and is associated with the formation of NO. Both the formation of NO and the stimulation of the soluble guanylate cyclase induced by L-arginine are enantiomer specific and abolished by L-MeArg. Thus, human platelets contain an NO synthase which is activated when platelets are stimulated. The consequent generation of NO modulates platelet reactivity by increasing cyclic GMP. Changes in the activity of this pathway in platelets may have physiological, pathophysiological, and therapeutic significance.
人洗涤血小板与胶原蛋白聚集时，伴随环鸟苷酸（cGMP）浓度依赖性增加，而环腺苷酸（cAMP）无此变化。NG-单甲基-L-精氨酸（L-MeArg）是一种从L-精氨酸合成一氧化氮（NO）的选择性抑制剂，可减少这种增加并增强聚集。L-精氨酸对cGMP基础水平无影响，但可增强胶原蛋白诱导的该核苷酸增加，还可抑制聚集。L-精氨酸的这两种作用均被L-MeArg减弱。L-精氨酸的抗聚集作用被前列环素和环鸟苷酸磷酸二酯酶的选择性抑制剂M&B22948增强，但不被环腺苷酸磷酸二酯酶的选择性抑制剂HL725增强。L-精氨酸也以类似方式抑制全血中的血小板聚集，尽管所需浓度要高得多。L-精氨酸刺激可溶性鸟苷酸环化酶并增加血小板胞质溶胶中的cGMP。这种刺激依赖于NADPH和Ca2+，并与NO的形成有关。L-精氨酸诱导的NO形成和可溶性鸟苷酸环化酶的刺激均具有对映体特异性，并被L-MeArg消除。因此，人血小板含有一种NO合酶，当血小板受到刺激时被激活。由此产生的NO通过增加cGMP来调节血小板反应性。血小板中该途径活性的变化可能具有生理、病理生理和治疗意义。
