Abstract

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)