Effect of cholecystokinin receptor antagonist on pancreatic responses to exogenous gastrin and cholecystokinin and to meal stimuli.
Exocrine pancreatic response to food is believed to result from the interaction of neural and hormonal factors, but their contribution in the net postprandial secretion is unknown. Recent description of a highly specific and potent cholecystokinin (CCK)-receptor antagonist permitted the evaluation of the physiologic role of CCK in postprandial pancreatic secretion. In dogs with chronic pancreatic fistula, CCK antagonism caused little alteration in sham feeding- or urecholine-induced pancreatic protein secretion, but reduced by approximately 60% the pancreatic protein response to a gastrointestinal meal and virtually abolished the pancreatic responses to duodenal perfusion with amino acids or oleate and to exogenous CCK, but not to secretin or neurotensin. The pancreatic protein responses, particularly to lower doses of gastrin, were also reduced by CCK-receptor antagonist, but no changes in the responses to secretin or neurotensin were detected. Cholecystokinin antagonism also significantly reduced the pancreatic polypeptide responses to CCK, gastrin, and the gastrointestinal meal, possibly due to removal of the CCK-mediated release of pancreatic polypeptide. We conclude that CCK plays a crucial role in the mediation of the gastrointestinal phase, but not the cephalic phase, of pancreatic secretion.
Konturek
S J
SJ
Institute of Physiology, Academy of Medicine, Krakow, Poland.
Tasler
J
J
Cieszkowski
M
M
Szewczyk
K
K
Hladij
M
M
D000818:Animals; D002766:Cholecystokinin / Q000502:physiology*; D004285:Dogs; D005502:Food; D005747:Gastric Fistula / Q000503:physiopathology; D005755:Gastrins / Q000494:pharmacology* / Q000502:physiology; D005973:Glutamine / Q000031:analogs & derivatives*; D010179:Pancreas / Q000378:metabolism*; D010185:Pancreatic Fistula / Q000503:physiopathology; D010191:Pancreatic Polypeptide / Q000378:metabolism; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects*
D005755:Gastrins; D011949:Receptors, Cholecystokinin; D005973:Glutamine; D010191:Pancreatic Polypeptide; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide