Effects of endogenous and exogenous cholecystokinin and of infusion with the cholecystokinin antagonist L-364,718 on pancreatic and gastrointestinal growth.
Continuous subcutaneous infusion of cholecystokinin (CCK-8; 5 micrograms/kg/h) to rats for 7 weeks raised the plasma CCK concentration almost fivefold and increased the pancreatic weight by about 50% but was without effect on the gastrointestinal tract. Continuous subcutaneous infusion of the CCK antagonist L-364,718 (200 micrograms/kg/h) for 7 weeks reduced the weight of the pancreas by about 30% but was without effect on the gastrointestinal tract. The effect of continuous subcutaneous infusion of CCK-8 and L-364,718 in combination was very similar to that of L-364,718 alone. Pancreaticobiliary diversion (PBD) induced a nearly 10-fold increase in the plasma CCK concentration 3 and 7 weeks after the operation. The serum gastrin values were unaffected. The weight of the pancreas was more than doubled after 7 weeks. At the same time the small intestine had gained weight, but the colon was unaffected. Continuous subcutaneous infusion of L-364,718 prevented the effect of PBD on the pancreas. On the basis of the assumption that L-364,718 is a specific antagonist of CCK, we conclude that endogenous CCK has a trophic effect on the pancreas but not on the gastrointestinal tract and that it is essential for normal pancreatic growth.
Axelson
J
J
Dept. of Surgery, University of Lund, Sweden.
Håkanson
R
R
Ihse
I
I
Lilja
I
I
Rehfeld
J F
JF
Sundler
F
F
D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D002766:Cholecystokinin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D020109:Devazepide; D004064:Digestive System / Q000187:drug effects / Q000254:growth & development*; D007263:Infusions, Parenteral; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000254:growth & development*; D051381:Rats; D011919:Rats, Inbred Strains
D001570:Benzodiazepinones; D002766:Cholecystokinin; D020109:Devazepide