Studies of monoamine oxidases: Inhibition of bovine brain MAO in intact mitochondria by selective inhibitors

Abstract

The inhibition of mitochondrial monoamine oxidase (MAO) from beef brain cortex by the selective inhibitors, clorgyline, harmaline, Deprenyl and pargyline, was compared using five substrates: serotonin (5-HT), β-phenylethylamine (PEA), tyramine, tryptamine and dopamine. Dose-response studies, consistent with the classification of MAO, types A and B, indicated that serotonin deamination was more sensitive to clorgyline and harmaline inhibition than was phenylethylamine. However, the curves for all substrates were double-sigmoidal, rather than being a single sigmoid curve for 5-HT and PEA. Deprenyl and pargyline did not exhibit any marked selectivity for inhibiting PEA deamination without prior preincubation of enzyme and inhibitor. The rate of inhibition was variable and was dependent upon the substrate, the nature of the inhibitor and the inhibitor concentration. Dual inhibitor studies, using the “type A” inhibitor, clorgyline, and the “type B” inhibitor, Deprenyl, together, resulted in almost complete MAO inhibition, regardless of substrate. Combining the two type A inhibitors, clorgyline and harmaline, or the two type B inhibitors, deprenyl and pargyline, resulted in inhibitions that were equal to or only slightly greater than the inhibition produced by a single inhibitor. These results suggested that there are at least two distinct sites in beef brain MAO from cortical mitochondria which may be interacting. The deamination of all substrates occurs at both sites.