Octreotide and cholecystokinin antagonist reduce edema in obstruction-induced acute pancreatitis.
Obstruction-induced acute pancreatitis in rats is associated with increased plasma cholecystokinin (CCK) levels. Duodenal replacement of bile reduces severity of pancreatitis and limits CCK increase. We investigated the role of CCK in the pathogenesis of obstruction-induced acute pancreatitis by pretreating rats with the somatostatin analog octreotide and the CCK antagonist L-364,718. Octreotide inhibits duodenal CCK release, and L-364,718 competitively blocks CCK receptors. We studied 31 rats after (1) sham operation (n = 7), (2) bile and pancreatic duct obstruction (BPDO) (n = 12), (3) BPDO plus octreotide (20 micrograms/kg IP and then 5 micrograms/kg/hr IV) (n = 6), and (4) BPDO plus L-364,718 (1 mg/kg IP and then 0.25 mg/kg/hr IV) (n = 6). Rats were killed after 18 hours. Pancreas weight, acute pancreatitis histology score, and plasma amylase and CCK levels were determined. Octreotide and L-364,718 limited the increase in pancreas weight. Octreotide also limited the rise in plasma CCK levels. These findings suggest that CCK may play a role in the pathogenesis of obstruction-induced acute pancreatitis.
Toriumi
Y
Y
Surgical and Research Services, Veterans Affairs Lakeside Medical Center, Chicago, IL 60611.
Samuel
I
I
Wilcockson
D P
DP
Turkelson
C M
CM
Solomon
T E
TE
Joehl
R J
RJ
D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology* / Q000627:therapeutic use; D001652:Bile Ducts; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004487:Edema; D008297:Male; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use; D010179:Pancreas / Q000187:drug effects / Q000473:pathology*; D010183:Pancreatic Ducts; D010195:Pancreatitis / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001570:Benzodiazepinones; D002766:Cholecystokinin; D020109:Devazepide; D015282:Octreotide