Direct and reversible inhibition of endothelial nitric oxide synthase by nitric oxide.
Direct and reversible inhibition of endothelial nitric oxide synthase by nitric oxide.
复制标题
一氧化氮对内皮一氧化氮合酶的直接和可逆抑制。
DOI：
10.1152/ajpheart.1995.268.6.h2216
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Rengasamy,A
中科院分区：
文献类型：
--
作者：
Ravichandran,LV;Johns,RA;Rengasamy,A
The objective of this study was to investigate the regulation of endothelial nitric oxide (NO) synthase by NO. Partially purified endothelial NO synthase was exposed to authentic NO (10-200 microM) and to the nitrovasodilators sodium nitroprusside (SNP; 10-1,000 microM) and S-nitroso-N-acetylpenicillamine (SNAP; 100-1,000 microM), and enzyme activity was assayed by measuring the conversion of L-[3H]arginine to L-[3H]citrulline in the presence of added cofactors. NO, SNP, and SNAP inhibited NO synthase activity in a dose-dependent manner, NO being the most potent inhibitor. The Michaelis constant for L-arginine was not altered (4.87 microM) by NO (50 microM), whereas the maximal velocity of the enzyme decreased from 784 to 633 pmol.mg-1.min-1. Oxyhemoglobin (10 microM) partially prevented the inhibition of NO synthase by NO (50 microM). The data also suggest that NO inhibits endothelial NO synthase activity by directly interacting with the NO synthase and not by an indirect mechanism such as limitation of cofactor or oxygen availability. Dialysis of NO synthase treated with NO (50 microM) partially restored the enzyme activity. This study demonstrates a direct and reversible inhibition of NO synthase by NO, suggesting a feedback mechanism in vivo.
