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Differential substrate specificity of monoamine oxidase in the rat heart and renal cortex

机译：大鼠心脏和肾皮质中单胺氧化酶的底物特异性差异

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Although it is known that substrate specificities differ with species and within each species with the tissues, in the rat heart no natural substrate was found for MAO-B. beta-phenylethylamine (beta-PEA) has always been considered the "endogenous" substrate of MAO B. We thought worthwide to evaluate the effect of Ro 41-1049 and lazabemide, both members of a class of highly selective, mechanism-based and reversible inhibitors for MAO-A and MAO B, respectively on the metabolization of beta-PEA by the rat heart. Also the lack of molecular data on rat heart MAOs, prompted us to better characterize rat heart MAOs, both kinetically and using molecular biology techniques. Km values for deamination of beta-PEA in the rat heart were 13-fold those in the kidney, by contrast, Km values for deamination of 5-HT were quite similar in both tissues. Unexpectedly, the selective MAO-A inhibitor Ro 41-1049 was by far the most potent inhibitor of beta-PEA (20 muM) deamination in the rat heart, while clorgyline, another MAO A inhibitor, and lazabemide, a MAO B inhibitor, had intermediate efficacy; selegiline was found unable to inhibit deamination of beta-PEA. In the rat renal cortex lazabemide and selegiline both inhibited beta-PEA deamination. The reduction of beta-PEA concentration to just 200 nM, the use of heart membranes instead of tissue homogenates or the use of heart membranes pre-treated with 1% digitonine failed to change this pattern of inhibition. Semicarbazide was found not to alter deamination of p-PEA. Western blot showed the presence of both isoforms (55 kd and 61 kd) in the renal cortex. In the heart there was a predominance of the A form, the B form being undetected. The RTPCR products for both MAO-A and MAO-B, were found to have the expected sizes. In conclusion, we found mRNA for MAO-B but were unable to detect the protein itself or its activity when using beta-PEA as the substrate. (C) 2003 Elsevier Science Inc. All rights reserved. [References: 41]
机译：尽管已知底物特异性随物种而异，并且在每个物种内随组织而异，但在大鼠心脏中未发现MAO-B的天然底物。 β-苯乙胺（β-PEA）一直被认为是MAO B的“内源性”底物。我们认为，值得一提的是评估Ro 41-1049和lazabemide的作用，这两种都是高度选择性，基于机制和可逆的成员分别是大鼠心脏对β-PEA代谢的MAO-A和MAO B抑制剂。此外，关于大鼠心脏MAO的分子数据的缺乏，促使我们从动力学和分子生物学技术上更好地表征大鼠心脏MAO。大鼠心脏中β-PEA脱氨基的Km值是肾脏的13倍，相比之下，两种组织中5-HT脱氨的Km值都非常相似。出乎意料的是，迄今为止，选择性MAO-A抑制剂Ro 41-1049是大鼠心脏中最有效的β-PEA脱氨抑制剂（20μM），而另一种MAO A抑制剂克洛基林和MAO B抑制剂lazabemide却具有这种作用。中等功效;发现司来吉兰不能抑制β-PEA的脱氨基。在大鼠肾皮质中，拉扎贝胺和司来吉兰均抑制β-PEA脱氨基。将β-PEA浓度降低至仅200 nM，使用心脏膜代替组织匀浆或使用经1％洋地黄碱预处理的心脏膜均无法改变这种抑制模式。发现氨基脲不改变对-PEA的脱氨基。 Western印迹显示肾皮质中同时存在两种同工型（55 kd和61 kd）。在心脏中，A形式占优势，B形式未被发现。发现用于MAO-A和MAO-B的RTPCR产品均具有预期的大小。总之，我们发现了MAO-B的mRNA，但是当使用β-PEA作为底物时无法检测到蛋白质本身或其活性。 （C）2003 Elsevier Science Inc.保留所有权利。 [参考：41]

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