title: Evidence for a functional coupling between dopamine reuptake and tyrosine hydroxylation in striatal nerve terminals.
abstract: In rat striatal synaptosomes incubated with [(14)C]tyrosine, the evolution of (14)CO(2), taken as a measure of dopamine synthesis, was inhibited by exogenous dopamine and by the dopaminergic receptor agonist ADTN. The inhibition was not counteracted by dopaminergic receptor antagonists (haloperidol, sulpiride, pimozide or domperidone). Instead, it was prevented by dopamine uptake blockers, suggesting that dopamine and ADTN (a substrate of the dopamine carrier) acted once inside the nerve endings and not through activation of autoreceptors on their external membrane. The dopamine uptake inhibitors nomifensine, benztropine and cocaine increased (14)CO(2) evolution from incubated striatal synaptosomes. Depolarization with KCl also increased dopamine synthesis and this action was potentiated when the reuptake of the released catecholamine was prevented by carrier blockers. The rate of dopamine synthesis was lowered when synaptosomal dopamine was raised upon incubation with monoamine oxidase inhibitors or with l-DOPA. The inhibition was counteracted by dopamine reuptake blockers. The data suggest that dopamine synthesis in striatal nerve endings is under the inhibitory control of the transmitter recaptured following release.
authors.affiliation: Istituto di Farmacologia e Farmacognosia, Università di Genova, Via Capo S. Chiara 5, 16146 Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Maura
authors.forename: M
authors.initials: M
authors.lastname: Raiteri