Protection against acute MPTP-induced dopamine depletion in mice by adenosine A1 agonist.
The effects of the adenosine A1 agonist N6-cyclohexyladenosine (CHA) on MPTP-induced dopamine (DA) depletion in the striatum of C57BL/6 mice were studied. Twenty hours after a single injection of MPTP (30 mg/kg, s.c.), the toxin caused 62% depletion of striatal DA. CHA (0.2-3 mg/kg, s.c.), when given together with MPTP, prevented the toxin-induced DA depletion in a dose-dependent manner. This protective action was apparently mediated by the A1 receptors, because this effect was selectively antagonized by pretreating the animals with the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (25 mg/kg, i.p.) but not with the A2 antagonist 1,3-dipropyl-7-methylxanthine (25 mg/kg, i.p.). When CHA (3 mg/kg) was injected 5 h after MPTP administration, at which point striatal DA levels were already reduced significantly, a rapid and complete recovery of the striatal DA levels occurred. These neurochemical data suggest that the A1 agonist CHA is potentially useful as a neuroprotective agent against MPTP-induced toxicity.
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Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska 68178.
Mouradian
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology
D011983:Receptors, Purinergic; D014970:Xanthines; C059953:1,3-dipropyl-7-methylxanthine; C027513:N(6)-cyclohexyladenosine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine