Reserpine prevents hydroxyl radical formation by MPP+ in rat striatum.
The present study investigated the blockage of dopamine (DA) oxidation by reserpine. 1-Methyl-4 phenylpyridinium ion (MPP+) increased the release of DA and the formation of hydroxyl radical ( r22. OH). The r22. OH generated by DA when captured as the hydroxylated derivative of salicylic acid was measured by the high-performance liquid chromatographic-electrochemical (HPLC-EC) procedure. MPP+ concentration for half-maximal effect of DA producing release (EC50) was 5.2 mM. The maximum attainable concentration of dialysate DA (Emax) by MPP+ was 7.7 microM. However, the EC50 and Emax values with reserpinized animal were 5.2 mM and 1.2 microM, respectively. When high concentration of pargyline (10 mM) were infused in MPP+ (5 mM)-pretreated animals, a marked elevation of DA and r22. OH formation was observed. The level of DA and 2, 3-DHBA formations was drastically reduced, as compared with the MPP+-only treated group. Although the levels of MPP+-induced DA and 2,3-DHBA formation after pargyline treatment increased, pargyline failed to increase either the level of MPP+-induced DA or 2,3-DHBA in the reserpinized group. When DA was administered to the MPP+-pretreatment group, a marked elevation was observed, showing a positive linear correlation DA and r22. OH formation trapped as 2,3-DHBA (R2=0.978) in the dialysate. When corresponding experiment were performed with iron (II), the same results were obtained: a positive linear correlation between the release of DA and 2,3-DHBA (R2=0.989) in the dialysate. These results indicated that reserpine-induced DA depletion may reduce MPP+-induced r22. OH formation.
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D062385:Hydroxybenzoates / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology*; D020156:Salicylic Acid / Q000378:metabolism; D013565:Sympatholytics / Q000494:pharmacology*