COMPARATIVE EFFECTS OF K-MUSCLE( CHANNEL MODULATING AGENTS ON CONTRACTIONS OF RAT INTESTINAL SMOOTH)

The effects of six K+ channel openers were investigated on contraction s of the rat ileum longitudinal muscle-myenteric plexus preparation el icited by electrical field stimulation and by K+. Levcromakalim, pinac idil, RP 49356 yl)-tetrahydro-thiopyran-2-carbothioamide-1-oxide) and SDZ PCO 400 lopenten-1-yl)oxy]-2H-1-benzopyran-6-carbonitrile) complet ely abolished contractions elicited by electrical stimulation and caus ed 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 agen ts were antagonized by glibenclamide, tetraethylammonium and yohimbine in a manner which was nor surmountable. The present study indicates t hat 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 dif ferences in the channels or their regulatory sites, in intestinal, com pared with vascular, smooth muscle.