Antagonism of receptors for gastrin, cholecystokinin and GRP/bombesin in postprandial stimulation of exocrine pancreas in dogs

Postprandial pancreatic secretion results from the interaction of neural and hormonal factors such as cholecystokinin (CCK), gastrin and gastrin releasing peptide (GRP), but their contribution to the net secretion is not established. Recent description of highly specific and potent hormonal receptor antagonists allows the determination of the physiological role of CCK, gastrin and GRP. In six dogs with chronic pancreatic fistulas, the blockade of CCK receptors by L-364, 718, gastrin receptors by L-365, 260 or GRP/bombesin receptors by nonapeptide RC-3095 failed to affect basal or sham-feeding induced pancreatic secretion indicating that none of these hormonal peptides plays a major role in this secretion. In contrast, the pancreatic response to ordinary feeding (which includes cephalic, gastric and intestinal phases), that was accompanied by a significant increment in plasma CCK and gastrin levels, was strongly inhibited (by over 50%) by L-364, 718 and slightly (by 20-30%) by L-365, 260 but not by RC-3095. Each antagonist was given at a dose that eliminated the secretory response to CCK, gastrin or GRP, respectively. We conclude that specific receptor antagonists are useful tools in assessing the physiological role of gut hormones in the control of pancreatic secretion and that none of the peptides tested appears to be involved in the cephalic phase. However, CCK plays a major role in the postprandial stimulation of pancreatic secretion.