Effect of L364 718 on interdigestive pancreatic exocrine secretion and gastroduodenal motility in conscious sheep

Abstract

The present study examined roles of endogenous cholecystokinin (CCK) and CCK-A receptors in the regulation of pancreatic exocrine secretion and gastroduodenal motility in conscious sheep during interdigestive period. Interdigestive exocrine secretion of ovine pancreas changed cyclically corresponding with cycle of duodenal migrating myoelectric complexes (MMC). During second phase of the duodenal MMC, intravenous injection of L364 718 at 2.45 μmol kg −1 inhibited exogenous CCK-8-induced pancreatic exocrine secretion. Intravenous infusion of the antagonist at 2.45 μmol kg −1/5 min for 5 min also inhibited significantly the pancreatic enzyme secretion without CCK-stimulation to half of that in the control, but not the fluid and bicarbonate secretion. Atropine infusion (i.v.) at 72.0 nmol kg −1/5 min significantly inhibited not only enzyme but also fluid and bicarbonate secretion. Corresponding to the inhibition of the exocrine secretion, L364 718 induced premature phase III in duodenal electromyogram (EMG) in three of the five sheep. Omasal EMG was inhibited slightly but significantly by L364 718, however, neither regular ruminal contractions nor abomasal EMG were altered by L364 718. In contrast, the atropine infusion inhibited only amplitude of ruminal contractions. These results suggest that endogenous CCK contributes to the regulation of interdigestive pancreatic exocrine secretion, omasal contractions and duodenal MMC in the ovine gastrointestinal tract via CCK-A receptors.