Effects of clanobutin on pancreatic secretion in vitro

The effects of clanobutin (4-[4-chloro-N-(4-methoxyphenyl)-benzamido]butyric acid) were investigated on two in vitro pancreatic preparations. In rat pancreatic lobules clanobutin (7.2 mM) stimulated the secretion of amylase and radiolabeled proteins to the same or higher extent as did CCK-PZ and carbachol in maximally active doses, but with a delay of 1-2 h. In the isolated rabbit pancreas clanobutin (3.3 mM) stimulated protein secretion about half as much as did carbachol, but without significant delay. The effect of clanobutin on protein secretion was prevented by prior application of carbachol, was not affected by the omission of Ca2+ from the medium and was only partly inhibited by the presence of atropine (0.1 mM). Prior addition of clanobutin did not prevent the effects of carbachol on enzyme secretion. In addition, clanobutin (3.3 mM) inhibited fluid secretion in the rabbit pancreas by about 50 percent; the inhibition was reversible. No effects on paracellular permeability were found with sucrose used as test substance. The findings indicate that clanobutin has opposite effects on enzyme and fluid secretion by rat and rabbit pancreas, which are not due to circulatory effects.