Feedback control of pancreatic secretion in rats. Role of gastric acid secretion.
Pancreatic secretion in rats is regulated by feedback inhibition of cholecystokinin (CCK) release by proteases in the gut lumen, but little is known about the role of gastric acid in this regulation. This study, carried out on conscious rats with large gastric fistulas (GF) and pancreatic fistulas, shows that diversion of pancreatic juice results in the progressive stimulation of pancreatic secretion only in rats with the GF closed. When the GF was kept open, the diversion resulted in only small increment in pancreatic secretion and this was accompanied by progressive increase in gastric acid outputs. Similar amounts of HCl instilled into the duodenum in rats with the GF open fully reproduced the increase in pancreatic secretion observed after the diversion of pancreatic juice. Pretreatment with omeprazole (15 mumol/kg) to suppress gastric acid secretion or with L-364,718 (5 mumol/kg) to antagonize CCK receptors in the diverted state, resulted in the decline in pancreatic secretion similar to that observed after opening the GF. CCK given s.c. (20-320 pmol/kg) failed to cause any significant rise in the post-diversion pancreatic secretion in rats with the GF closed, but stimulated this secretion dose-dependently when the GF was open. Camostate (6-200 mg/kg) in rats with pancreatic juice returned to the duodenum caused dose-dependent increase in pancreatic secretion, but after opening the GF or after omeprazole this increase was reduced by about 75%. This study provides evidence that gastric acid plays a crucial role in the pancreatic response to diversion of pancreatic juice or inhibition of luminal proteases, and that factors that eliminate gastric acid secretion reduce this response.
Bilski
J
J
Institute of Physiology, University School of Medicine, Kraków, Poland.
Konturek
P K
PK
Krzyzek
E
E
Konturek
S J
SJ
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism; D020109:Devazepide; D004952:Esters; D005246:Feedback / Q000502:physiology; D016670:Gabexate / Q000031:analogs & derivatives*; D005744:Gastric Acid / Q000378:metabolism* / Q000502:physiology; D005747:Gastric Fistula; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D010185:Pancreatic Fistula; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D001570:Benzodiazepinones; D004952:Esters; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D016670:Gabexate; D002766:Cholecystokinin; D020109:Devazepide; D009853:Omeprazole