1988 Volume 9 Issue 6 Pages 429-436
The effects of recently developed nonpeptide cholecystokinin (CCK) antagonists L-364, 718 and CR 1392 on pancreatic exocrine secretion were studied in both isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, both L-364, 718 and CR 1392 caused a concentration-dependent rightward shift of the dose-response curve for amylase secretion stimulated by CCK octapeptide (CCK-8) without altering the maximal increase. Both antagonists significantly inhibited amylase release in response to CCK-8 and caerulein but had no effect on amylase release stimulated by other receptor secretagogues or by agents bypassing receptors. L-364, 718 and CR 1392 added 20 min after the CCK-8 stimulation rapidly abolished pancreatic exocrine secretions in the isolated perfused pancreas. The suppressive effects of these antagonists on pancreatic exocrine secretion persisted even after the terminations of their infusion. These results indicate that both L-364, 718 and CR 1392 are extremely patent, competitive, specific and longacting antagonists of CCK in rat pancreas. These compounds are thus suitable for investigations on the physiological and pharmacological actions of CCK.
