Role of type A and type B monoamine oxidase in the metabolism of released [3H]dopamine from rat striatal slices

The effects of selective inhibition of multiple forms of monoamine oxidase (MAO) on the in vitro release and metabolism of newly-synthesized [³H]dopamine (DA) were examined using rat brain slices. Striatal slices were preincubated in the presence of [³H]l-tyrosine (20 μM) followed by a short incubation period in the presence of the selective irreversible MAO-inhibitor agents clorgyline (type A) and deprenyl (type B). Tissue pretreated in this manner was then subjected to a release incubation, and DA release and metabolism were determined under spontaneous and depolarizing conditions. Pretreatment with clorgyline (10^?7 M) significantly reduced the spontaneous, as well as K⁺-evoked, formation of both 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Deprenyl (10^?7 M) pretreatment did not significantly affect these variables, but clorgyline + deprenyl pretreatment resulted in a reduction of both DOPAC and HVA that was greater than that produced by clorgyline alone. By contrast, deprenyl pretreatment significantly decreased both DOPAC and HVA under depolarizing conditions, but only in the presence of the DA uptake inhibitor nomifensine (10^?5 M). In the absence of MAO inhibition, nomifensine increased K⁺-evoked formation of DOPAC and HVA, while spontaneous formation was not affected. The results suggest that released DA is deaminated primarily by the type A form of MAO; however, in the absence of the type A MAO, or under conditions that promote exclusive postsynaptic deamination, minor but significant metabolism occurs via the type B enzyme. Data obtained are further discussed in relation to the mechanism of MAO-inhibitor drug action and pre- versus postsynaptic formation of DOPAC and HVA.