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首页> 外文期刊>Life sciences >The activity of MAO A and B in rat renal cells and tubules.
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The activity of MAO A and B in rat renal cells and tubules.

机译：大鼠肾细胞和肾小管中MAO A和B的活性。

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摘要

The present study reports on the presence of type A and B monoamine oxidase (MAO) activity and their sensitivity to selective MAO-A and MAO-B inhibition by Ro 41-1049 and lazabemide, respectively, in homogenates of isolated rat renal tubules. Non-linear analysis of the saturation curve of H-5-hydroxytryptamine (3H-5-HT ) deamination revealed a Km of 351+/-71 microM (n=4) and a Vmax of 25+/-2 nmol mg protein(-1) h(-1). Deamination of 14C-beta-phenylethylamine (14C-beta-PEA) was also a saturable process yielding Km values of 58+/-12 microM and Vmax values of 24+/-2 nmol mg protein(-1) h(-1). Ro 41-1049 produced a concentration-dependent inhibition of 3H-5-HT deamination with a Ki of 24 nM. Deamination of 14C-beta-PEA was found to be reduced by lazabemide in a concentration-dependent manner with a Ki value of 17 nM. The effect of these selective MAO inhibitors on dopamine fate and DOPAC formation in isolated tubular epithelial cells was also studied. In these studies a clear inhibition of DOPAC formation was observed with Ro 41-1049 (250 nM), while 250 nM lazabemide was found not to increase the accumulation of newly-formed DA in those tubular epithelial cells loaded with 50 microM L-DOPA. In conclusion, the results presented here confirm the presence of both MAO-A and MAO-B activity in renal tubular epithelial cells, that MAO-A is the predominant enzyme involved in the deamination of the natriuretic hormone dopamine and that the deamination of newly-formed dopamine is a time-dependent process which occurs early after the decarboxylation of L-DOPA.
机译：本研究报道了在分离的大鼠肾小管匀浆中分别存在Ro 41-1049和lazabemide对A和B型单胺氧化酶（MAO）活性的存在及其对选择性MAO-A和MAO-B抑制的敏感性。对H-5-羟基色胺（3H-5-HT）脱氨基的饱和曲线进行非线性分析，发现Km为351 +/- 71 microM（n = 4），Vmax为25 +/- 2 nmol mg蛋白（ -1）h（-1）。 14C-β-苯乙胺（14C-β-PEA）的脱氨基也是一个可饱和的过程，其Km值为58 +/- 12 microM，Vmax值为24 +/- 2 nmol mg蛋白（-1）h（-1） 。 Ro 41-1049产生浓度依赖性的3H-5-HT脱氨抑制作用，Ki为24 nM。发现Lazabemide以浓度依赖性的方式减少了14C-β-PEA的脱氨基，Ki值为17 nM。还研究了这些选择性MAO抑制剂对分离的肾小管上皮细胞中多巴胺命运和DOPAC形成的影响。在这些研究中，用Ro 41-1049（250 nM）观察到了对DOPAC形成的明显抑制，而发现250 nM拉扎贝胺不会增加那些装有50 microM L-DOPA的肾小管上皮细胞中新形成的DA的积累。总之，此处介绍的结果证实了肾小管上皮细胞中同时存在MAO-A和MAO-B活性，MAO-A是利尿钠多巴胺脱氨过程中的主要酶，而新近形成的多巴胺是一个随时间变化的过程，发生在L-DOPA脱羧后的早期。

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