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A and B Forms of Monoamine Oxidase Within the Monoaminergic Neurons of the Rat Brain
Authors:Ingrid Fagervall  Svante B Ross
Institution:Department of Biochemical Neuropharmacology, Research Laboratories, Astra Läkemedel AB, Södertälje, Sweden
Abstract:The inhibition of the A and B forms of monoamine oxidase (MAO) inside and outside serotonergic, noradrenergic, and dopaminergic synaptosomes in homogenates of rat hypothalamus or striatum by clorgyline, a selective and irreversible MAO-A inhibitor, and selegiline, a selective and irreversible MAO-B inhibitor, was examined. Intrasynaptosomal deamination at low concentrations of the substrates 14C]5-hydroxytryptamine (14C]5-HT; 0.1 microM), 14C]noradrenaline (0.25 microM), 14C]3,4-dihydroxyphenylethylamine (14C]dopamine; 0.25 microM), and 14C]tyramine (0.25 microM) was hindered by selective uptake inhibitors (citalopram, maprotiline, and amfonelic acid) in the incubation media. Thus, the difference between the deamination of 14C-amine in the absence and presence of the appropriate selective uptake inhibitor provided a measure of deamination in the specific aminergic synaptosomes. This was verified by determining the loss of MAO activity within noradrenergic and serotonergic systems after degeneration of the nerve terminals by the neurotoxins N-chloroethyl-N-ethyl-2-bromobenzylamine and p-chloroamphetamine. Results with the two inhibitors revealed that the A and B forms were responsible for 80 and 20%, respectively, of the deamination of 14C]5-HT within serotonergic synaptosomes from the hypothalamus. The deamination of 14C]noradrenaline within the noradrenergic synaptosomes from the hypothalamus and that of 14C]dopamine and 14C]tyramine within the striatal dopaminergic synaptosomes were due to MAO-A. About 10% of the deamination of 14C]noradrenaline, 14C]dopamine, and 14C]tyramine outside the noradrenergic or dopaminergic synaptosomes was brought about by the B form, with the remainder being deaminated by MAO-A.
Keywords:3  4-Dihydroxyphenylethylamine  5-Hydroxytryptamine  Hypothalamus  Monoamine oxidase  Noradrenaline  Striatum
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