title: Regulation of striatal enkephalin turnover in rats receiving antagonists of specific dopamine receptor subtypes.
abstract: The hypothesis that striatal dopamine regulates enkephalin (ENK) synthesis is supported by the increase of striatal proenkephalin mRNA and ENK after intranigral injection of 6-hydroxydopamine. In order to elucidate which dopamine receptor subtype is operative in the regulation of the dynamic state of ENK, the effect of drugs that block D-1 or D-2 receptor selectively was studied. Daily administration of 140 mumol/kg s.c. of the D-2 antagonist I-sulpiride twice daily for 2 weeks produces a 30% decrease in the content of striatal proenkephalin mRNA and ENK. In contrast, a 50% increase was observed after 2 weeks of treatment with the D-1 antagonist SCH 23390 at 74 nmol/kg s.c. three times a day. Hence, it can be inferred that the endogenous activation of D-1 tonically decreases striatal ENK synthesis. Removal of this neurally mediated regulation either by a specific pharmacologic blockage of D-1 or by lesioning with 6-hydroxydopamine increases the biosynthesis of ENK. The increase of ENK biosynthesis elicited by denervation with 6-hydroxydopamine cannot be due to the endogenous activation of D-2 receptors and must be due to the inactivation of the tonic inhibition exerted by D-1 receptors.
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D006892:Hydroxydopamines; D008297:Male; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D004745:Enkephalins; D006892:Hydroxydopamines; D011498:Protein Precursors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; C029992:proenkephalin; D013469:Sulpiride; D016627:Oxidopamine