Effects of non-peptidal CCK receptor antagonist (L-364,718) on pancreatic responses to cholecystokinin, gastrin, bombesin, and meat feeding in dogs.
Postprandial pancreatic secretion results from the interaction of neural and hormonal factors but their contribution to the net postprandial secretion is unknown. Recent description of highly specific and potent cholecystokinin (CCK) receptor antagonists allows the determination of the physiological role of CCK in the postprandial pancreatic secretion. In six dogs with chronic pancreatic fistulae, the blockade of CCK receptors by non-peptidal agent (L-364,718) caused little change in basal pancreatic secretion, but decreased significantly (p less than 0.05) by about 60% the pancreatic protein response to meat feeding and virtually abolished the pancreatic responses to CCK-8 and bombesin. The pancreatic protein responses to pentagastrin, reaching about 37% of CCK maximum, was also significantly reduced but this effect was less pronounced than that observed in tests with CCK-8 or bombesin stimulation. In contrast, cholinergically stimulated pancreatic secretion, reaching about 40% of CCK maximum, was unaffected by L-364,718. Cholecystokinin antagonism also failed to affect the postprandial and bombesin induced increments in plasma CCK and gastrin concentrations, but significantly reduced the PP responses to CCK-8 bombesin and meat feeding possibly as a result of the removal of the CCK mediated release of PP. We conclude that CCK plays a crucial role in the mediation of the postprandial and bombesin induced pancreatic secretion and in the PP release.
Konturek
S J
SJ
Institute of Physiology, Academy of Medicine, Krakow, Poland.
Tasler
J
J
Konturek
J W
JW
Cieszkowski
M
M
Szewczyk
K
K
Hładij
M
M
Anderson
P S
PS
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism; D001839:Bombesin / Q000037:antagonists & inhibitors*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004285:Dogs; D004435:Eating; D005755:Gastrins / Q000037:antagonists & inhibitors*; D008460:Meat; D010179:Pancreas / Q000187:drug effects*; D010191:Pancreatic Polypeptide / Q000097:blood; D011506:Proteins / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology
D001570:Benzodiazepinones; D001639:Bicarbonates; D005755:Gastrins; D011506:Proteins; D010191:Pancreatic Polypeptide; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide; D001839:Bombesin