EMD 52692 (bimakalim), a new potassium channel opener, attenuates luminol-enhanced chemiluminescence and superoxide anion radical formation by zymosan-activated polymorphonuclear leukocytes.
We investigated the relationship of potassium channel activation on modulation of oxidative respiratory bursts in canine neutrophils. Generation of superoxide anion radicals in opsonized zymosan-activated cells was determined using the technique of ferricytochrome c reduction. Preincubation of cells with the selective potassium channel opener, EMD 52692 (1-100 microM), attenuated superoxide anion radical production. Furthermore, EMD 52692 also produced a concentration-dependent inhibition of luminol-enhanced chemiluminescence by activated neutrophils. Glyburide, a selective antagonist of ATP-sensitive potassium channels, prevented the modulatory effect of EMD 52692 on both superoxide anion generation and luminol-enhanced chemiluminescence. The results suggest that ATP-sensitive potassium channels may play a significant role in regulating oxygen-derived free radical production in neutrophil-induced tissue injury.
Pieper
G M
GM
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Gross
G J
GJ
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D015221:Potassium Channels / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
D001578:Benzopyrans; D004095:Dihydropyridines; D015221:Potassium Channels; D014665:Vasodilator Agents; D013481:Superoxides; C061050:bimakalim; D015054:Zymosan