Effect of cholecystokinin and its antagonists lorglumide, devazepide, and L-365,260 on gastrointestinal motility in rats

Cholecystokinin (CCK) plays an important role in gallbladder contraction and gut motility. Sincalide (CCK-8) evoked guinea pig isolated ileum contraction at 10(-5)-10(-1) mumol.L-1 in a concentration-dependent manner, EC50 being 207 pmol.L-1. It delayed the gastric emptying as well. The rate of inhibition of gastric emptying was 71 +/- 12% at 100 micrograms.kg-1 by ip. Sincalide antagonists: lorglumide, devazepide, and L-365,260 antagonized the ileal smooth muscle response to sincalide in a concentration-dependent manner. Their pA2 were 7.30, 10.02, and 7.77, respectively. Lorglumide, devazepide, and L-365,260 inhibited the delaying of gastric emptying evoked by sincalide. The IC50 were 0.11, 0.0064, and 0.66 mg.kg-1, respectively.