Effects of cromakalim on acetylcholine release and smooth muscle contraction in guinea-pig small intestine.
The effects of the potassium channel opener cromakalim on smooth muscle contraction and 3H-acetyl-choline release were studied simultaneously in guinea-pig longitudinal muscle myenteric plexus preparations which had been preincubated with 3H-choline. Cromakalim (10 mumol/l) inhibited more markedly the smooth muscle contractions caused by the release of endogenous acetylcholine (via electrical stimulation or via activation of nicotine- and 5-HT3-receptors) than contractions induced by pilocarpine. Cromakalim (10 mumol/l) did not affect the release of 3H-acetylcholine evoked by electrical stimulation or by stimulation of nicotine- and 5-HT3-receptors. In contrast, the release of 3H-acetylcholine caused by stimulation of M1-receptors was concentration-dependently reduced by cromakalim (1-100 mumol/l). The results suggest that the relaxant effect of cromakalim on smooth muscle contraction is not caused by a reduction of acetylcholine release from myenteric neurones. An opening of cromakalim-sensitive potassium channels may be involved in the inhibition of the M1-receptor mediated acetylcholine release.
Department of Pharmacology, University of Mainz, Federal Republic of Germany.
H
H
Schwörer
H
H
Kilbinger
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*
D001578:Benzopyrans; D011758:Pyrroles; D019806:Cromakalim; D000109:Acetylcholine