Opening of ATP-sensitive K(+) (KATP) channels enhance hydroxyl radical generation induced by MPP(+) in rat striatum.
The present study examined whether opening of adenosine triphosphate (ATP) sensitive K(+) (KATP) channels can enhance 1-methyl-4-phenylpyridinium (MPP(+))-induced hydroxyl radical (OH) generation in rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5nmol/ml per min) was infused through a microdialysis probe to detect the generation of OH as reflected by the non-enzymatic formation of 2.3-dihydroxybenzoic acid (DHBA) in the striatum. MPP(+) (5mM) enhanced generation of OH with concomitant increased efflux of dopamine (DA). Cromakalim (100μM), a KATP channel opener, through the microdialysis probe significantly increased both DA efflux and OH formation induced by MPP(+). Another KATP channel opener, nicorandil (1mM), also increased the level DA or DHBA, but these changes were not significant. However, in the presence of glibenclamide (10μM), a KATP channel antagonist, and the increase of MPP(+)-induced DA or DHBA were not observed. Cromakalim (10, 50 and 100μM) increased MPP(+)-induced DHBA formation in a concentration-dependent manner. However, the effects of cromakalim in the presence of glibenclamide were abolished. These results suggest that opening of KATP channels may cause OH generation by MPP(+).
['Obata|Toshio|T|', 'Nakashima|Michiko|M|']
D000818:Animals D003342:Corpus Striatum D019806:Cromakalim D004298:Dopamine D004305:Dose-Response Relationship, Drug D005905:Glyburide D062385:Hydroxybenzoates D017665:Hydroxyl Radical D054086:KATP Channels D020267:MPTP Poisoning D008297:Male D049990:Membrane Transport Modulators D017551:Microdialysis D020108:Nicorandil D017208:Rats, Wistar
Cromakalim Nicorandil 1-Methyl-4-phenylpyridinium ion (MPP(+)) ATP-sensitive K(+) (K(ATP)) channel Free radicals Parkinson's disease