title: Dopamine biosynthesis is regulated by the amine newly recaptured by dopaminergic nerve endings.
abstract: The synthesis of dopamine from labeled tyrosine (but not from labeled DOPA) in rat striatal synaptosomes was effectively inhibited by exogenous dopamine only when the amine was allowed to enter the nerve endings. In the presence of the uptake blocker nomifensine, extracellular dopamine was almost inactive. The evolution of 14CO2 from [14C]tyrosine was consistently higher when synaptosomes were 'incubated' in the presence of nomifensine than in its absence. This effect disappeared when synaptosomes were 'superfused' with labeled tyrosine (with or without nomifensine) in conditions in which dopamine reuptake cannot occur. The monoaminoxidase inhibitor pargyline inhibited 14CO2 evolution from [14C]tyrosine. However, the effect was almost abolished if dopamine reuptake was prevented (by nomifensine or in superfusion). Our results suggest that dopaminergic nerve endings do not possess autoreceptors controlling dopamine synthesis. In the present paper it is proposed that the regulation of dopamine synthesis occurs through inhibition of tyrosine hydroxylase, according to the classical and end-product concept; however, the function of 'end-product' would be primarily exerted by the amine newly taken up by the nerve terminals.
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis* / Q000502:physiology; D005246:Feedback; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D009627:Nomifensine; D010293:Pargyline; D001058:Apomorphine; D004298:Dopamine