Calcium channel agonist, (+/-)-Bay K8644, causes an immediate increase in the striatal 1-methyl-4-phenylpyridinium level following systemic administration of the dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, in Balb/c mice.
In vivo formation of 1-methyl-4-phenylpyridinium ion (MPP(+)) in the striatum, and dopaminergic neurotoxicity following systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the presence and absence of calcium channel agonist (+/-)-Bay K8644 were analyzed in Balb/c mice. We used HPLC-photodiode array detection, HPLC-electrochemical detection and spectrofluorimetric procedures to measure striatal MPP(+) and dopamine (DA) and for the assay of monoamine oxidase-B (MAO-B) activity, respectively. Systemic administration of (+/-)-Bay K8644 resulted in a significant increase in striatal MAO-B activity. An MPTP-induced decrease in striatal MAO-B activity was attenuated by pre-treatment with (+/-)-Bay K8644 initially, but not on the 3rd day. MPP(+) formation in the striatum following systemic administration of MPTP was significantly increased by the pre-treatment of the agonist initially (30 min), but was not different afterwards (at 60 and 90 min). Nevertheless, the total MPP(+) formed over a 90 min period was found to be comparable. (+/-)-Bay K8644 administration prior to MPTP failed to influence the MPTP-induced striatal DA depletion on the 3rd day. While the transient effect of (+/-)-Bay K8644 on striatal MAO-B is reflected as an immediate increase in the levels of MPP(+) in the striatum, it failed to affect MPTP-induced DA neurotoxicity in Balb/c mice.
Samantaray
Supriti
S
Division of Neurosciences, Indian Institute of Chemical Biology, 4, Raja S C Mullick Road, Jadavpur, Calcutta 700 032, India.
Mohanakumar
Kochupurackal P
KP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage*; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism*; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity; D004357:Drug Synergism; D051379:Mice; D008807:Mice, Inbred BALB C
D002120:Calcium Channel Agonists; D015259:Dopamine Agents; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium