FORMATION OF NITRIC-OXIDE FROM L-ARGININE IN THE CENTRAL NERVOUS-SYSTEM - A TRANSDUCTION MECHANISM FOR STIMULATION OF THE SOLUBLE GUANYLATE-CYCLASE
FORMATION OF NITRIC-OXIDE FROM L-ARGININE IN THE CENTRAL NERVOUS-SYSTEM - A TRANSDUCTION MECHANISM FOR STIMULATION OF THE SOLUBLE GUANYLATE-CYCLASE
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DOI：
10.1073/pnas.86.13.5159
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发表时间：
1989-07-01
影响因子：
11.1
通讯作者：
MONCADA, S
中科院分区：
文献类型：
--
作者：
KNOWLES, RG;PALACIOS, M;MONCADA, S
一种从大鼠前脑获得的可溶性酶，催化L-精氨酸生成一氧化氮（NO）和瓜氨酸的NADPH依赖性形成。形成的NO刺激可溶性鸟苷酸环化酶，这种刺激被低浓度的血红蛋白消除。NO和瓜氨酸的合成依赖于生理浓度的游离Ca 2+的存在，并且被NG-单甲基-D-精氨酸抑制，但不被其对映体NG-单甲基-D-精氨酸或L-刀豆氨酸抑制。L-高精氨酸、L-天冬氨酸酯或L-精氨酸甲酯可以代替L-精氨酸作为酶的底物。这些结果表明，NO是从L-精氨酸在大脑中通过类似的血管内皮细胞，中性粒细胞和巨噬细胞中的酶反应形成的，增加了支持我们的假设，即NO从L-精氨酸的形成是一个广泛的转导机制的可溶性鸟苷酸环化酶的刺激。
A soluble enzyme obtained from rat forebrain catalyzes the NADPH-dependent formation of nitric oxide (NO) and citrulline from L-arginine. The NO formed stimulates the soluble guanylate cyclase and this stimulation is abolished by low concentrations of hemoglobin. The synthesis of NO and citrulline is dependent on the presence of physiological concentrations of free Ca2+ and is inhibited by NG-monomethyl-D-arginine, but not by its enantiomer NG-monomethyl-D-arginine or by L-canavanine. L-Homoarginine, L-arginyl-L-aspartate, or L-arginine methyl ester can replace L-arginine as substrates for the enzyme. These results indicate that NO is formed from L-arginine in the brain through an enzymic reaction similar to that in vascular endothelial cells, neutrophils, and macrophages, adding support to our hypothesis that the formation of NO from L-arginine is a widespread transduction mechanism for the stimulation of the soluble guanylate cyclase.