Effects of Novel Potassium Channel Opener KR-30450 and its Metabolite KR-30818 on the Smooth, Muscle of the Guinea Pig

The effect of potassium channel openers, KR-30450, KR-30818 and lemakalim have been compared against several spasmogens in guinea pig bronchi. In guinea pig bronchi, KR-30450 had a greater relaxant effect than lemakalim and KR-30818 against tone induced by histamine $10^{-5}M$ ($EC_{50}$ $\mu$M: KR-30450, 0.108$\pm$0.077; KR-30818, 0.403$\pm$0.023; lemakalim, 0.968$\pm$0.036) and prostaglandin $F_{2\alpha} 3\times10^{-6} M$ ($EC_{50}$ $\mu$M: KR-30450, 0.018$\pm$0.001; KR-30818, 0.028$\pm$0.003; lemakalim, 0.138$\pm$0.019). Relaxant effect of KR-30450 and KR-30818 were significantly reduced by 20 min pretreatment of tissues with $10^[-6}$ M glibenclamide, a selective blocker of ATP-sensitive potassium channel. Against acetylcholine-induced tone in guinea pig bronchi, however, these compounds had little effect. In summary, KR-30450 and KR-30818 showed greater relaxant effect than lemakalim in guinea pig bronchi (KR-30450>KR-30818>lemakalim). These relaxant actions are suggested to be mediated at least in part by a mechanism which involves the opening of ATP-sensitive potassium channel.