Cromakalim inhibits transmitter acetylcholine release in rat trachea by an action on epithelial cells and a diffusible factor

The present study was undertaken to investigate further the effects of the potassium channel opening drug cromakalim on the release of transmitter acetylcholine from cholinergic nerves of rat isolated trachea by using two tracheal preparations superfused in series. In all experiments, the lower chamber contained an epithelium-denuded preparation which had been incubated with [3H]-choline to incorporate [3H]-acetylcholine into cholinergic transmitter stores, whereas the upper chamber contained an unlabelled, epithelium-intact or epithelium-denuded preparation. When the upper chamber contained an epithelium-intact tracheal preparation, cromakalim (1-100 µM) significantly reduced the stimulation-induced (S-I) efflux of [3H]-acetylcholine from the radiolabelled, epithelium-denuded tracheal preparation in the lower flow chamber. In contrast, when the upper flow chamber contained an epithelium-denuded preparation, cromakalim (10 µM) was without effect on the S-I efflux. Glibenclamide (1 µM), an ATP-sensitive potassium channel blocker, was without effect on the S-I efflux when the upper chamber contained an unlabelled, epithelium-intact tracheal preparation.