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儿茶酚胺第8位上的氚标记所引入的误差。

Errors introduced by a tritium label in position 8 of catecholamines.

作者信息

Grohmann M, Henseling M, Cassis L, Trendelenburg U

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1986 Jan;332(1):34-42. doi: 10.1007/BF00633194.

Abstract

The neuronal and extraneuronal disposition of 3H-7,8- and 3H-7-labelled (-)-noradrenaline and dopamine was compared in in vitro studies. In agreement with earlier studies, the present results show that the presence of a tritium label in position 8 (i.e., on the alpha-carbon) has two consequences: a) the rate of deamination declines and b) part of the deamination results in the formation of an unlabelled aldehyde plus tritium water; tritium water is recovered from the OMDA-fraction of the column chromatographic procedure of Graefe et al. (1973). Whenever the deamination of a 3H-catecholamine is reduced (by tritium in position 8), the intraneuronal 3H-catecholamine concentration is increased. This increase, in turn, partly masks the decline in neuronal deamination (rat vas deferens). Irrespective of whether one determines the spontaneous efflux, the release of 3H-noradrenaline by nerve stimulation or the release of 3H-(-)-noradrenaline by the reserpine-like compound Ro 4-1284, the presence of tritium in position 8 distorts the results (experiments with rat vasa deferentia and/or rabbit aorta). In the extraneuronal system of the rat heart, two intracellular enzymes inactivate 3H-(-)-noradrenaline and 3H-dopamine: catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO). Any hindrance of deamination (by tritium in position 8, COMT intact) leads to a shift of the metabolism of the 3H-catecholamines from the exclusively deaminated to the exclusively O-methylated metabolites. No differences between 3H-7,8- and 3H-7-labelled catecholamines were found after inhibition of MAO and COMT (extraneuronal accumulation and rate constant for efflux from the extraneuronal compartment III of the rat heart).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在体外研究中比较了3H-7,8-和3H-7标记的(-)-去甲肾上腺素和多巴胺的神经元内和神经元外分布。与早期研究一致,目前的结果表明,8位(即α-碳上)存在氚标记有两个后果:a)脱氨基速率下降;b)部分脱氨基导致形成未标记的醛加氚水;氚水可从Graefe等人(1973年)柱色谱法的OMDA部分回收。每当3H-儿茶酚胺的脱氨基作用降低(8位有氚)时,神经元内3H-儿茶酚胺浓度就会增加。反过来,这种增加部分掩盖了神经元脱氨基作用的下降(大鼠输精管)。无论测定的是自发外流、神经刺激释放的3H-去甲肾上腺素还是利血平样化合物Ro 4-1284释放的3H-(-)-去甲肾上腺素,8位存在氚都会使结果失真(大鼠输精管和/或兔主动脉实验)。在大鼠心脏的神经元外系统中,两种细胞内酶使3H-(-)-去甲肾上腺素和3H-多巴胺失活:儿茶酚-O-甲基转移酶(COMT)和单胺氧化酶(MAO)。脱氨基作用的任何阻碍(8位有氚,COMT完整)都会导致3H-儿茶酚胺的代谢从仅脱氨基代谢物转变为仅O-甲基化代谢物。在抑制MAO和COMT后,未发现3H-7,8-和3H-7标记的儿茶酚胺之间存在差异(大鼠心脏神经元外区室III的神经元外积累和外流速率常数)。(摘要截短于250字)

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