Comparative effects of K+ channel modulating agents on contractions of rat intestinal smooth muscle

The effects of six K+ channel openers were investigated on contractions of the rat ileum longitudinal muscle-myenteric plexus preparation elicited by electrical field stimulation and by K+. Levcromakalim, pinacidil, RP 49356 (N-methyl-2-(3-pyridyl)-tetrahydro-thiopyran-2-carbothioamide-1-oxide) and SDZ PCO 400 ((3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-[(3-oxo-1-cyclopenten-1-yl)oxy]-2H-1-benzopyran-6-carbonitrile) completely abolished contractions elicited by electrical stimulation and caused complete relaxation of contractions elicited by K+ with comparable IC50 values. Minoxidil sulphate was much less potent and diazoxide was without effect in either protocol. The relaxant effects of these agents were antagonized by glibenclamide, tetraethylammonium and yohimbine in a manner which was nor surmountable. The present study indicates that the relaxant effect of these compounds in intestinal smooth muscle is mediated through glibenclamide-sensitive ATP-dependent K+ channels. These compounds did not preferentially inhibit either direct smooth muscle- or nerve-mediated responses. The present data may point to differences in the channels or their regulatory sites, in intestinal, compared with vascular, smooth muscle.