Types A and B monoamine oxidase contribute to the metabolism of norepinephrine in perfused lungs of rats.
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)
Westwood
N N
NN
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
Bryan-Lluka
L J
LJ
D000818:Animals; D003641:Deamination; D005260:Female; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000493:pharmacokinetics; D010477:Perfusion; D010848:Picolinic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000201:enzymology
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; D013844:Thiazoles; C063456:Ro 41-1049; C059303:lazabemide; D008995:Monoamine Oxidase; D009638:Norepinephrine