Bryan-Lluka L J
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
Naunyn Schmiedebergs Arch Pharmacol. 1995 Apr;351(4):408-16. doi: 10.1007/BF00169082.
Previous studies on the pulmonary removal and metabolism of catecholamines in rat lungs have shown that, when the lungs are perfused with a low concentration (1 nmol/l) of noradrenaline, the amine is metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), but is predominantly O-methylated, and the activities of COMT and MAO are 0.357 min-1 and 0.186 min-1, respectively. The aim of the present study was to examine the changes in the metabolic profile of noradrenaline in rat lungs over a range of concentrations, and to examine the kinetics of the pulmonary O-methylation of noradrenaline and adrenaline. In isolated lungs perfused with 3H-noradrenaline, there was a progressive decrease in the proportion of O-methylated metabolites and a corresponding increase in the proportion of deaminated metabolites, as the noradrenaline concentration in the perfusion solution was increased from 1 to 10 to 100 to 1000 nmol/l. Experiments designed to determine the rate of uptake of noradrenaline in lungs perfused with 1 nmol/l 3H-noradrenaline, under conditions of MAO inhibited, COMT inhibited and COMT and MAO inhibited, showed that the results were compatible with co-existence of COMT and MAO in the pulmonary endothelial cells. Hence, it appeared that the changing metabolic profile with amine concentration in the previous series of experiments was not due to saturation of noradrenaline uptake into cells that contained COMT but not MAO.(ABSTRACT TRUNCATED AT 250 WORDS)
先前关于大鼠肺脏中儿茶酚胺的肺清除及代谢的研究表明，当用低浓度（1纳摩尔/升）的去甲肾上腺素灌注肺脏时，该胺类物质会被儿茶酚-O-甲基转移酶（COMT）和单胺氧化酶（MAO）代谢，但主要是O-甲基化，且COMT和MAO的活性分别为0.357分钟⁻¹和0.186分钟⁻¹。本研究的目的是检测去甲肾上腺素在大鼠肺脏中一系列浓度范围内代谢谱的变化，并检测去甲肾上腺素和肾上腺素肺O-甲基化的动力学。在用³H-去甲肾上腺素灌注的离体肺脏中，随着灌注液中去甲肾上腺素浓度从1纳摩尔/升增加到10纳摩尔/升、100纳摩尔/升再到1000纳摩尔/升，O-甲基化代谢物的比例逐渐降低，脱氨基代谢物的比例相应增加。在MAO抑制、COMT抑制以及COMT和MAO均抑制的条件下进行的旨在测定用1纳摩尔/升³H-去甲肾上腺素灌注的肺脏中去甲肾上腺素摄取速率的实验表明，结果与COMT和MAO在肺内皮细胞中共存相符。因此，在前一系列实验中胺浓度变化时代谢谱的改变似乎并非由于去甲肾上腺素摄取到含有COMT但不含MAO的细胞中达到饱和所致。（摘要截短于250词）
