Inhibition of mitochondrial monoamine oxidase of the rat uterus and liver by clorgyline, pargyline and harmine

Abstract

The inhibition of mitochondrial monoamine oxidase (MAO) activity in rat uterus and liver by clorgyline, harmine and pargyline is reported. MAO activity is shown to be present in mitochondria of the rat uterus by rate-zonal centrifugation on a sucrose gradient. Each inhibitor was tested for its ability to inhibit the oxidation of tyramine (TYN). 5-hydroxytryptamine (5HT) and β-phenylethylamine (PEA). TYN deamination by uterine organelles was inhibited in two distinct steps by clorgyline and harmine, whereas in liver mitochondria only clorgyline manifested the two-step inhibition pattern. Elimination of TYN oxidation by pargyline occurred as a single sigmoid curve. Single sigmoid inhibition curves with all three inhibitors were also observed for 5HT and PEA in both tissues. For uterine and liver mitochondria the relative effectiveness of each inhibitor toward the oxidation of the three substrates was as follows: (a) clorgyline and harmine. 5HT > TYN > PEA; (b) pargyline. PEA > TYN > 5HT. It was concluded that, as has been previously demonstrated in liver, two forms of MAO exist in mitochondria isolated from the rat uterus. This conclusion is based upon (1) the biphasic inhibition of TYN deamination by clorgyline and harmine and (2) the reversal of the relative inhibitory effectiveness of the two classes of MAO inhibitors, (a) clorgyline and harmine and (b) pargyline, toward the three substrates. Semicarbazide did not inhibit the oxidation of any of the substrates. This indicates that the mitochondrial enzyme activity from the uterus, as in the liver, is a true monoamine oxidase.