Chen L Y, Mehta J L
Department of Medicine, University of Florida, Gainesville, USA.
J Pharmacol Exp Ther. 1996 Jan;276(1):253-7.
L-Arginine analogs are generally used as inhibitors of nitric oxide (NO) synthesis in a variety of tissues. We studied the effects of two analogs of L-arginine on L-arginine transport and NO synthase activity in human polymorphonuclear leukocytes (PMN) and platelets. Both NG-nitro-L-arginine methylester and N omega-nitro-L-arginine reduced the uptake of 3H-L-arginine in human PMN and platelets in a concentration-dependent fashion. The inhibitory effect of these analogs on the uptake of 3H-L-arginine was greater in PMN than in platelets (P < .05). Both agents also modestly inhibited NO synthase activity in platelet cytosol, whereas neither had significant and specific effect on NO synthase activity in the PMN cytosol. NO synthase activity in intact PMN, but not in platelets, was insensitive to exogenous Ca++. Reverse transcription-polymerase chain reaction products showed the presence of endothelial constitutive (756 bp) and the neuronal constitutive (629 bp) NO synthase isoforms in human platelets and PMN, respectively. This was further confirmed by Southern analysis. Thus the classic inhibitors of NO synthesis primarily decrease L-arginine uptake in PMN and platelets, and significantly affect NO synthase activity only in platelets. These differences may, at least in part, be due to the presence of different NO synthase isoform in platelets and PMN.
L-精氨酸类似物通常被用作多种组织中一氧化氮（NO）合成的抑制剂。我们研究了两种L-精氨酸类似物对人多形核白细胞（PMN）和血小板中L-精氨酸转运及一氧化氮合酶活性的影响。NG-硝基-L-精氨酸甲酯和Nω-硝基-L-精氨酸均以浓度依赖性方式降低人PMN和血小板对3H-L-精氨酸的摄取。这些类似物对3H-L-精氨酸摄取的抑制作用在PMN中比在血小板中更强（P <.05）。两种药物还适度抑制血小板胞质溶胶中的一氧化氮合酶活性，而对PMN胞质溶胶中的一氧化氮合酶活性均无显著的特异性影响。完整PMN中的一氧化氮合酶活性对外源Ca++不敏感，而血小板中的则敏感。逆转录-聚合酶链反应产物显示，人血小板和PMN中分别存在内皮型组成性（756 bp）和神经元型组成性（629 bp）一氧化氮合酶同工型。Southern分析进一步证实了这一点。因此，经典的一氧化氮合成抑制剂主要降低PMN和血小板中L-精氨酸的摄取，且仅显著影响血小板中的一氧化氮合酶活性。这些差异可能至少部分归因于血小板和PMN中存在不同的一氧化氮合酶同工型。
