On the pharmacological and physiological role of glibenclamide-sensitive potassium channels in colonic smooth muscle.
Actions of activators of glibenclamide sensitive K+ channels on canine colonic circular muscle were investigated. Cromakalim as well as its (-) enantiomer lemakalim caused inhibition of spontaneous phasic contractile activity (EC50's 4.4 +/- 0.1 x 10(-7) M and 2.3 +/- 0.4 x 10(-7) M, respectively) and of carbachol induced activity (EC50's: 9.4 +/- 5.1 x 10(-7) M and 4.3 +/- 1.4 x 10(-7) M, respectively). Cromakalim and lemakalim effects were completely inhibited by glibenclamide. Additive effects between K+ channel activators and other drugs relaxing colonic muscle (the L-type calcium channel blocker D600 and forskolin) were seen. A physiological role for specific glibenclamide sensitive K+ channels, if existing, remains unresolved. The present study indicates that the non-adrenergic inhibitory nerves do not act through these channels, neither does stimulation of muscarinic or beta-adrenergic receptors.
Richardson
D
D
McMaster University, Department of Biomedical Sciences, Hamilton, Ontario, Canada.
Alibhai
K N
KN
Huizinga
J D
JD
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects; D019806:Cromakalim; D004285:Dogs; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013237:Stereoisomerism
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D005576:Colforsin; D005711:Gallopamil; D002217:Carbachol; D005905:Glyburide