AJP - Gastrointestinal and Liver Physiology, Vol 256, Issue 1 150-G157, Copyright © 1989 by American Physiological Society

ARTICLES

Comparative effects of CCK receptor antagonists on rat pancreatic secretion in vivo

M. Niederau, C. Niederau, G. Strohmeyer and J. H. Grendell
Medizinische Klinik und Poliklinik, Universitat Dusseldorf, Federal Republic of Germany.

The present experiments evaluate in vivo effects of recently described cholecystokinin (CCK) receptor antagonists on rat pancreatic secretion. Pancreaticobiliary secretion was studied after bile duct cannulation in anesthetized rats. After two basal 10-min fractions were selected, secretion was stimulated by intravenous caerulein (0.1-30.0 micrograms/kg) or secretin, and collected for seven further 10-min fractions. Peptide antagonists (CR 1409, CR 1392, and CR 1505) and nonpeptide antagonists (asperlicin and L364,718) were given intravenously 10 min before agonists. Increasing doses of antagonists gradually reduced secretion of protein and enzymes stimulated by submaximal and maximal doses of caerulein. The antagonists did not alter nonstimulated or secretin-stimulated secretion, indicating their specificity for the CCK receptor. Except for proglumide and asperlicin, all antagonists were able to abolish caerulein-stimulated pancreatic secretion, as evaluated by the mean integrated 1-h response to a near-maximal dose of caerulein. The caerulein dose-response curve was gradually shifted to the right by increasing doses of CR 1409, indicating competitive-like kinetics. Inhibition of secretion due to supramaximal doses of caerulein, however, could be reversed by doses of CR 1409 smaller than expected from extrapolating truely competitive kinetics from an in vitro situation to the in vivo situation. The rank order of potency of the compounds to antagonize caerulein-stimulated secretion in vivo agreed with their relative potencies to antagonize caerulein-stimulated amylase secretion from pancreatic acini in vitro as well as with their affinity to bind to peripheral CCK receptors in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				Y. Li, X. Y. Wu, J. X. Zhu, and C. Owyang Intestinal serotonin acts as paracrine substance to mediate pancreatic secretion stimulated by luminal factors Am J Physiol Gastrointest Liver Physiol, October 1, 2001; 281(4): G916 - G923. [Abstract] [Full Text] [PDF]

				Y. Li, J. Zhu, and C. Owyang Electrical physiological evidence for highand low-affinity vagal CCK-A receptors Am J Physiol Gastrointest Liver Physiol, August 1, 1999; 277(2): G469 - G477. [Abstract] [Full Text] [PDF]

				M. Yamamoto, H. Shirohara, and M. Otsuki CCK-, secretin-, and cholinergic-independent pancreatic fluid hypersecretion in protease inhibitor-treated rats Am J Physiol Gastrointest Liver Physiol, February 1, 1998; 274(2): G406 - G412. [Abstract] [Full Text] [PDF]