Decrease in rat striatal dopamine synthesis and metabolism in vivo by metabolically stable adenosine receptor agonists.
The administration of the stable adenosine analog (R)-N-(1-methyl-2-phenylethyl)adenosine (R-PIA) caused a dose-dependent decrease in the accumulation of striatal dihydroxyphenylalanine (DOPA) levels following DOPA decarboxylase inhibition, with the minimum effective dose being 0.2 mg/kg, i.p.; 5'-deoxy-5'-(ethylamino)-5'-oxoadenosine (NECA) at 0.5 mg/kg, i.p., was also active indicating that in vivo R-PIA and NECA were decreasing striatal dopamine (DA) synthesis. Both R-PIA and NECA also decreased striatal levels of the DA metabolite 3-methoxytyramine (3-MT), indicating a decreased release of DA which was consistent with their effects on DA synthesis. N-Cyclohexyladenosine (CHA) also decreased 3-MT levels. The S-isomer of PIA at an equipotent dose did not affect either DA synthesis or release. R-PIA (3 mg/kg, i.p.) antagonized the pargyline-induced increase in striatal 3-MT levels as did gamma-butyrolactone, further confirming a decreased release of striatal DA. The adenosine receptor antagonist 8-cyclopentyltheophylline antagonized the R-PIA induced-decrease in striatal DA synthesis, suggesting that the latter was mediated via adenosine receptors. It is concluded that the stable adenosine analogs R-PIA and NECA, at behaviorally active doses, are decreasing in vivo the rate of DA synthesis and release from rat striatal DA nerve terminals by an adenosine receptor-mediated effect.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D011983:Receptors, Purinergic
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D004295:Dihydroxyphenylalanine; D000241:Adenosine; D004298:Dopamine