Cholecystokinin antagonist prevents hyperamylasemia and improves pancreatic exocrine function in cerulein-induced acute pancreatitis.
Supramaximal cerulein administration induces acute pancreatitis, which markedly impairs pancreatic secretion in conscious rats. We hypothesized that pretreatment with the potent cholecystokinin antagonist, L-364,718, improves the pancreatic secretory impairment associated with cerulein-induced acute pancreatitis. Rats were surgically prepared with gastric, duodenal, bile, and pancreatic fistulas and jugular vein catheters. On postoperative day 4, groups of rats were administered (a) L-364,718 1 mg/kg intraduodenally, (b) cerulein 5 micrograms/kg/h for 6 h intravenously, (c) L-364,718 1 mg/kg intraduodenally followed by cerulein 5 micrograms/kg/h for 6 h intravenously, and (d) safflower oil carrier intraduodenally. On postoperative day 5, we studied cholecystokinin (CCK)-stimulated pancreatic secretion. Plasma amylase was measured at the time of surgery and at the conclusion of experiments on postoperative days 4 and 5. The duodenally administered CCK antagonist had no effect, 24 h later, on CCK-evoked protein secretion and prevented the pancreatic exocrine impairment and hyperamylasemia caused by supramaximal cerulein administration. These observations suggest that cerulein-induced acute pancreatitis is mediated by a CCK-receptor mechanism.
Murayama
K M
KM
Surgical Service, VA Lakeside Medical Center, Chicago, IL 60611.
Drew
J B
JB
Nahrwold
D L
DL
Joehl
R J
RJ
D000208:Acute Disease; D000681:Amylases / Q000097:blood*; D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism; D002108:Ceruletide; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004386:Duodenum; D010179:Pancreas / Q000187:drug effects / Q000503:physiopathology*; D010189:Pancreatic Juice / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology
D001570:Benzodiazepinones; D001639:Bicarbonates; D002108:Ceruletide; D002766:Cholecystokinin; D000681:Amylases; D020109:Devazepide; D012844:Sincalide