METABOLISM OF AMINES BY MITOCHONDRIAL MONOAMINE OXIDASE AND SUBSTRATE SELECTIVITY

Abstract

We studied the metabolism of amines by mitochondrial monoamine oxidase (MAO) and substrate selectivity in mammalian brain. The following conclusions were obtained. 1) The regional distribution of MAO-B in human brain by autoradiographical use of 11C-L-deprenyl was high in the caudate nucleus, putamen, thalamus, substantia nigra.The half-life for the turnover rate of MAO-B in pig brain by positron emission tomography using 11C-L-deprenyl was calculated to be 6.5 days. 2) Relation between serotonin and dopamine uptake rates, monoamine concentrations and MAO activities were estimated in various regions of rat brain. Of main interest is the finding that MAO activities in general (conventional method) were positively correlated to seroton in uptake rates and to intra-5-HT-synaptosomal MAO, but not to dopamine uptake rates or intra-DA-synaptosomal MAO activities. 3) An inhibition of MAO-B of more than 40 % was required to reduce the MPTP toxicity and it was completely prevented at about 60 % MAO inhibition. Moreover, although MPTP toxicity in relation to age, dopamine up take and MAO activity was investigated in two rodent species, MAO-B activity was not the rate-limiting step for MPTP neurotoxicity. 4) Histamine H3-ligands inhibited the conversion of N-tele-methylhistamine to N-tele-methylimidazoleacetic acid by MAO-B in the rat brain.5) The oxidation of racemic chlorpheniramine was catalyzed by mitochondrial MAO of rat brain. Moreover, there was a stereoselective difference in oxidative deamination of chlorpheniramine by MAO-A and -B.