K+ channel openers relax longitudinal muscle of guinea pig ileum

The plexus-free longitudinal muscle was used to investigate the muscle-relaxing effects of the known K+ channel openers, cromakalim, pinacidil and nicorandil, and compared with other known muscle relaxants, calcitonin gene-related peptide (CGRP) and isoprenaline. The three K+ channel openers all decreased basal tension and inhibited the tonic tension evoked by 30 mM KCl, 0.5 microM histamine or 0.1 microM oxotremorine in a dose-dependent manner. The order of potency is cromakalim > pinacidil > nicorandil in KCl or oxotremorine-precontracted muscle strip and nicorandil > cromakalim > pinacidil in histamine-precontracted muscle strip. Inhibition by cromakalim was completely reversed by glibenclamide, a blocker of ATP-sensitive K+ channels, while inhibition by nicorandil or pinacidil was only partially antagonized. The tonic tension evoked by KCl, histamine or oxotremorine was relaxed by CGRP or isoprenaline. Inhibition by neither of these compounds was relieved by glibenclamide. These results suggest that while ATP-sensitive K+ channels may be present in the longitudinal muscle cells, they may not be involved in the actions of CGRP or isoprenaline on the longitudinal muscle.