Westwood N N, Bryan-Lluka L J
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
J Pharmacol Exp Ther. 1993 Nov;267(2):815-21.
The aim of the study was to determine the activity of monoamine oxidase (MAO) and the contributions of the A and B forms of MAO to the metabolism of norepinephrine (NE) in isolated perfused lungs of the rat. Preliminary experiments to investigate the MAO-A and MAO-B selective inhibitors, Ro41-1049 and Ro19-6327, respectively, were carried out in isolated preparations of rat vas deferens incubated in 10 nM [3H]NE (Uptake2 and catechol-O-methyltransferase inhibited) to measure rates of deamination of NE and the rate constant for deamination (kMAO) by MAO-A. These experiments showed that 1) the IC50 of Ro41-1049 for inhibition of MAO-A was 9.62 nM with 97% inhibition by 300 nM and 2) 100 or 300 nM Ro19-6327 did not affect deamination of NE by MAO-A. Hence, 300 nM Ro41-1049 and 100 nM Ro19-6327 were used to inhibit selectively MAO-A and MAO-B, respectively, in rat lungs perfused in vitro with 10 nM [3H]NE. Catechol-O-methyltransferase was inhibited and kMAO values for metabolism of NE were determined. The kMAO value for deamination of NE in the absence of Ro41-1049 or Ro19-6327 was 0.186 min-1. Ro41-1049 and Ro19-6327 decreased this kMAO value by 79 and 33%, respectively. Thus, it was concluded that both MAO-A and MAO-B contribute to the deamination of NE in the pulmonary circulation of the rat, with MAO-A responsible for 67-79% of the total deamination and MAO-B for 21-33%.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是测定大鼠离体灌注肺中去甲肾上腺素（NE）代谢过程中，单胺氧化酶（MAO）的活性以及MAO A型和B型对NE代谢的贡献。分别用MAO-A和MAO-B选择性抑制剂Ro41-1049和Ro19-6327进行的初步实验，是在10 nM [3H]NE（摄取2和儿茶酚-O-甲基转移酶被抑制）孵育的大鼠输精管离体标本中进行的，以测量NE的脱氨速率和MAO-A的脱氨速率常数（kMAO）。这些实验表明：1）Ro41-1049抑制MAO-A的IC50为9.62 nM，300 nM时抑制率为97%；2）100或300 nM的Ro19-6327不影响MAO-A对NE的脱氨作用。因此，在体外灌注10 nM [3H]NE的大鼠肺中，分别用300 nM Ro41-1049和100 nM Ro19-6327选择性抑制MAO-A和MAO-B。抑制儿茶酚-O-甲基转移酶，并测定NE代谢的kMAO值。在不存在Ro41-1049或Ro19-6327时，NE脱氨的kMAO值为0.186 min-1。Ro41-1049和Ro19-6327分别使该kMAO值降低了79%和33%。因此得出结论，MAO-A和MAO-B均参与大鼠肺循环中NE的脱氨作用，其中MAO-A占总脱氨作用的67-79%，MAO-B占21-33%。（摘要截选至250字）
