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(+).
School of Nursing, Faculty of Health Sciences, Osaka Aoyama University, 2-11-1 Niina, Mino City, Japan. Electronic address: t-obata@osaka-aoyama.ac.jp.
Toshio
T
Obata
Department of Nursing, School of Health Sciences, Asahi University, 1851 Hozumi, Mizuho City, Gifu, Japan.
Michiko
M
Nakashima
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D019806:Cromakalim / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D054086:KATP Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D017551:Microdialysis; D020108:Nicorandil / Q000494:pharmacology; D017208:Rats, Wistar
D062385:Hydroxybenzoates; D054086:KATP Channels; D049990:Membrane Transport Modulators; D019806:Cromakalim; D020108:Nicorandil; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D005905:Glyburide; D004298:Dopamine
1-Methyl-4-phenylpyridinium ion (MPP(+)); ATP-sensitive K(+) (K(ATP)) channel; Cromakalim; Free radicals; Nicorandil; Parkinson's disease