AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 3 347-G352, Copyright © 1985 by American Physiological Society
Role of cholecystokinin in pancreatic exocrine response to intraluminal amino acids and fat
R. S. Stubbs and B. E. Stabile
Controversy continues over the relative contributions made by hormonal and
neural mechanisms in the exocrine pancreatic response to ingested food. The
recent description of the drug proglumide as a specific, competitive
cholecystokinin (CCK)/gastrin receptor antagonist has permitted
reevaluation of the role of CCK in this process. In chronic pancreatic
fistula dogs, dose-response studies were performed to determine the effect
of proglumide on the pancreatic responses to octapeptide of CCK (CCK-OP),
intravenous bethanechol, intraduodenal amino acids, and intraduodenal fat.
Pancreatic volume, protein, and bicarbonate outputs to all doses of CCK-OP
were inhibited significantly (P less than 0.05) in a competitive manner,
consistent with the proposed mode of action of proglumide. In contrast,
proglumide caused only minor and insignificant inhibition of the output
responses to intravenous bethanechol. Virtually complete inhibition to all
doses of intraduodenal amino acids and fat was observed with proglumide
administration. If indeed proglumide is a specific CCK receptor antagonist,
these results support the hypothesis that CCK is the major mediator of the
intestinal phase of exocrine pancreatic secretion.
