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Nitric oxide inhibits tyrosine hydroxylase of rat median eminence

机译:一氧化氮抑制大鼠中位突出酪氨酸羟化酶

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Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of catecholamines. In a previous report we found that intracerebroventricular administration of nitric oxide (NO) generator sodium nitroprusside (SNP) to conscious male rats inhibited dose-dependently the TH activity of the median eminence (ME). In the present study we have tested the in vitro effects of SNP on TH activity, its possible mediator and action mechanism. Exposure of the ME TH to SNP (50, 100 and 500 mu M) caused concentration-dependent inhibition of its enzyme activity. Addition of; reduced hemoglobin Hb (10 mu M), a NO scavenger, superoxide dismutase SOD (1000 units/ml), a superoxide scavenger enzyme or uric acid UA (300 mu M), a peroxynitrite scavenger, did not affect the enzyme activity by themselves, but prevented the inhibitory effect of SNP 500 mu M. However, the presence of methylene blue MB (100 mu M), a guanylyl cyclase inhibitor, did not alter either basal enzyme activity or the inhibitory action of SNP 500 mu M. These results suggest that this action of SNP on TH of the ME would be mediated by peroxynitrite generated by the reaction of NO with superoxide. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 18]
机译:酪氨酸羟化酶(TH)是儿茶酚胺生物合成中的限速酶。在以前的报告中,我们发现对有意识的雄性大鼠脑室内给予一氧化氮(NO)生成器硝普钠(SNP),其剂量依赖性地抑制了中位隆起(ME)的TH活性。在本研究中,我们测试了SNP对TH活性,可能的介体和作用机制的体外作用。将ME TH暴露于SNP(50、100和500μM)会引起其酶活性的浓度依赖性抑制。外加的;减少的血红蛋白Hb(10μM),NO清除剂,超氧化物歧化酶SOD(1000单位/ ml),超氧化物清除剂酶或过氧化亚硝酸盐清除剂尿酸UA(300μM)本身不会影响酶的活性,但是阻止了SNP 500μM的抑制作用。但是,鸟苷酸环化酶抑制剂亚甲基蓝MB(100μM)的存在不会改变基础酶活性或SNP 500μM的抑制作用。这些结果表明SNP对ME TH的这种作用将由NO与超氧化物反应生成的过氧亚硝酸盐介导。 (C)2000 Elsevier Science Inc.保留所有权利。 [参考:18]

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