Role of cholecystokinin in the intestinal fat- and acid-induced inhibition of gastric secretion.
This study was designed to determine the role of cholecystokinin (CCK) in the inhibition of gastric HCl secretion by duodenal peptone, fat and acid in dogs with chronic gastric and pancreatic fistulas. Intraduodenal instillation of 5% peptone stimulated both gastric HCl secretion and pancreatic protein secretion and caused significant increments in plasma gastrin and CCK levels. L-364,718, a selective antagonist of CCK-A receptors, caused further increase in gastric HCl and plasma gastrin responses to duodenal peptone but reduced the pancreatic protein outputs in these tests by about 75%. L-365,260, an antagonist of type B receptors, reduced gastric acid by about 25% but failed to influence pancreatic response to duodenal peptone. Addition of 10% oleate or acidification of peptone to pH 3.0 profoundly inhibited acid secretion while significantly increasing the pancreatic protein secretion and plasma CCK levels. Administration of L-364,718 reversed the fall in gastric HCl secretion and significantly attenuated pancreatic protein secretion in tests with both peptone plus oleate and peptone plus acid. Exogenous CCK infused i.v. in a dose (25 pmol/kg per h) that raised plasma CCK to the level similar to that achieved by peptone meal plus fat resulted in similar inhibition of gastric acid response to that attained with fat and this effect was completely abolished by the pretreatment with L-364,718. We conclude that CCK released by intestinal peptone meal, containing fat or acid, exerts a tonic inhibitory influence on gastric acid secretion and gastrin release through the CCK-A receptors.
Konturek
S J
SJ
Institute of Physiology, Academy of Medicine, Krakow, Poland.
Bilski
J
J
Cieszkowski
M
M
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001626:Bethanechol Compounds / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D020109:Devazepide; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula; D005755:Gastrins / Q000097:blood; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D010185:Pancreatic Fistula; D010461:Peptones / Q000494:pharmacology*; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000494:pharmacology
D001570:Benzodiazepinones; D001626:Bethanechol Compounds; D005755:Gastrins; D009829:Oleic Acids; D010461:Peptones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D019301:Oleic Acid; C058121:L 365260; D006632:Histamine; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide