Gross S S, Stuehr D J, Aisaka K, Jaffe E A, Levi R, Griffith O W
Department of Pharmacology, Cornell University Medical College, New York, N.Y. 10021.
Biochem Biophys Res Commun. 1990 Jul 16;170(1):96-103. doi: 10.1016/0006-291x(90)91245-n.
Many cell types are known to synthesize nitric oxide (NO.) from L-arginine. There appear to be at least two forms of NO. synthase: an inducible, tetrahydrobiopterin- and flavin-dependent activity exemplified by the macrophage enzyme and a constitutive, Ca+(+)-dependent activity exemplified by the endothelial cell enzyme. L-NG-methylarginine inhibits NO. synthesis by both cell types. We now report that L-NG-aminoarginine and L-NG-nitroarginine are about 100-fold more potent than NG-methylarginine in blocking endothelial cell NO. synthesis. In contrast, NG-aminoarginine and NG-methylarginine are about equipotent with macrophages whereas NG-nitroarginine is much less potent. Since macrophage and endothelial cell NO. synthesis are differentially sensitive to the inhibitors, the panel of inhibitors can be used in complex biological systems to determine if macrophage-like or endothelial-like cells are the predominant source of NO.. Indeed, all three inhibitors elicit a strong pressor response in the anesthetized guinea pig, a result consistent with the view that endothelial cells continually produce vasodilatory NO(.).
已知许多细胞类型可从L-精氨酸合成一氧化氮（NO.）。似乎至少有两种形式的NO.合酶：一种是诱导型的，以巨噬细胞酶为代表的依赖四氢生物蝶呤和黄素的活性，另一种是组成型的，以内皮细胞酶为代表的依赖Ca+(+)的活性。L-NG-甲基精氨酸可抑制这两种细胞类型的NO.合成。我们现在报告，L-NG-氨基精氨酸和L-NG-硝基精氨酸在阻断内皮细胞NO.合成方面比NG-甲基精氨酸强约100倍。相比之下，NG-氨基精氨酸和NG-甲基精氨酸对巨噬细胞的作用大致相当，而NG-硝基精氨酸的作用则弱得多。由于巨噬细胞和内皮细胞的NO.合成对这些抑制剂的敏感性不同，因此可以在复杂的生物系统中使用这组抑制剂来确定巨噬细胞样或内皮细胞样细胞是否是NO.的主要来源。事实上，所有这三种抑制剂在麻醉的豚鼠中都会引发强烈的升压反应，这一结果与内皮细胞持续产生血管舒张性NO(.)的观点一致。
