Administration of Two Antagonists of the Cholecystokinin B /Gastrin Receptor Does Not Totally Inhibit the Pancreatic Response to a Meal in the Pig

Abstract

We suggest that the stimulation of pancreatic protein secretion by a meal is not mediated by CCK(B)/gastrin receptors. Because we previously showed that the CCK(A)receptor antagonist MK329 was no more able to abolish this response, CCK is probably not responsible for this response.

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

“…This led to the conclusion that the information driven by CCK must be switched into a neural mechanism before leaving the gut. This indirect mechanism agrees with the facts that amylase release from human pancreatic acinar cells is not mediated by either the CCK 1 or CCK 2 receptor in vitro (Miyasaka et al 2002) and that the administration of antagonists of the CCK 2 receptor does not totally inhibit the in vivo pancreatic response to a meal in the pig (Lhoste et al 2002). Moreover, if we consider the classic hypothesis of hormonal action of CCK via the blood, we must keep in mind, first, that the blood plasma contains enzymes, endopeptidases and aminopeptidases, capable of deactivating CCK (Deschodt-Lanckman et al 1983), and second, that the intestinal blood promptly transports these newly released gut peptides to the liver, an important site of gut peptide deactivation.…”

Cholecystokinin and Gastrin Receptors

“…CCK and gastrin stimulate pancreatic secretion in calves via both CCK1R and CCK2R but CCK1R, although not predominantly expressed, seems to play a major role (272). CCK2R was also found to predominate in the pig pancreas where a proportion of 70% CCK2R and 30% CCK1R was estimated; however, the functional role of CCK2R in pig pancreatic secretion remains uncertain (146,279,375). These data raise the question of which functions are under the control of the CCK2R in the exocrine pancreas.…”