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.