Mediation of trypsin inhibitor-induced pancreatic hypersecretion by secretin and cholecystokinin in rats.
We investigated a hormonal mechanism in a trypsin inhibitor-induced pancreatic hypersecretion in rats. Intraduodenal administration of a synthetic trypsin inhibitor, camostat, resulted in significant increases in plasma concentration of both secretin and cholecystokinin in a dose-related manner that paralleled a significant increase in exocrine pancreatic secretion. To eliminate the effect of circulating secretin in rats, a rabbit antisecretin serum was given IV that resulted in a 77% reduction in bicarbonate secretion stimulated by intraduodenal camostat. A cholecystokinin receptor antagonist, MK-329, also inhibited significantly the camostat-induced increase in pancreatic secretion; volume and bicarbonate output were reduced by 35% each and amylase output by 73%. The combined administration of antisecretin serum and MK-329 completely abolished the pancreatic exocrine secretion stimulated by camostat. These observations indicate that the camostat-stimulated pancreatic exocrine secretion is mediated by the increased release of both secretin and cholecystokinin in rats.
Watanabe
S
S
Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical College, Japan.
Takeuchi
T
T
Chey
W Y
WY
D000704:Analysis of Variance; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology*; D007106:Immune Sera; D016018:Least-Squares Analysis; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012633:Secretin / Q000097:blood / Q000276:immunology / Q000502:physiology*; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D001570:Benzodiazepinones; D004952:Esters; D006146:Guanidines; D007106:Immune Sera; D014361:Trypsin Inhibitors; C034532:camostat; D012633:Secretin; D016670:Gabexate; D002766:Cholecystokinin; D020109:Devazepide