Different roles for type A and type B monoamine oxidase in regulating synaptic dopamine at D-1 and D-2 receptors associated with adenosine-3',5'-cyclic monophosphate (cyclic AMP) formation.

Abstract

The roles of multiple forms of monoamine oxidase (MAO) in regulating the synaptic concentration of dopamine, in the vicinity of dopamine receptors associated with cyclic AMP formation, was examined in striatal slices of the rat. d-Amphetamine (0.1 mumol/l to 20 mumol/l) caused a concentration-related increase in cyclic AMP formation, which correlated (in superfusion experiments) with the release of endogenously-formed dopamine. In the presence of (-)sulpiride (50 mumol/l), cyclic AMP formation was significantly increased at every concentration of d-amphetamine tested. At the same time, this concentration of (-)sulpiride had no effect on DA release. Inhibition of type A MAO with clorgyline (0.1 mumol/l) significantly enhanced the increase in cyclic AMP formation seen after d-amphetamine. By contrast, inhibition of type B MAO with deprenyl (0.1 mumol/l) was without effect on this action of d-amphetamine. At high concentrations of d-amphetamine (20 mumol/l), however, deprenyl + clorgyline treatment enhanced cyclic AMP formation to a greater extent than with clorgyline alone. Similar results could be obtained at lower concentrations of d-amphetamine (5 mumol/l), but only after inhibition of the dopamine neuronal reuptake system with nomifensine (30 mumol/l). Furthermore, in the presence of nomifensine, deprenyl alone was also able to significantly increase the cyclic AMP formation seen after d-amphetamine (5 mumol/l). In the presence of (-)sulpiride, relatively similar results were obtained following all MAO inhibitor treatments. These findings support the notion that type A MAO plays the primary role in regulating dopamine concentrations at D-1 and D-2 receptors within synapses of rat striatal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)