Effects of L-364,718, a new cholecystokinin receptor antagonist, on camostate-induced growth of the rat pancreas.
Chronic feeding of rats with camostate results in pancreatic hypertrophy or hyperplasia, or both. Previous studies suggest that this effect of camostate occurs via an increase in endogenous cholecystokinin due to an enteral feedback mechanism involving the inhibition of trypsin in the duodenum. Studies employing proglumide, a weak and relatively nonspecific cholecystokinin antagonist, have failed to fully abolish camostate-induced pancreas growth. We examined the effects of L-364,718, a new and highly potent cholecystokinin receptor antagonist, on camostate-induced pancreas growth in rats. The pancreas weights and the concentrations of ribonucleic acid, protein, and chymotrypsinogen in the pancreas of rats treated with camostate alone were significantly elevated over those of controls. These effects of camostate were completely abolished in rats treated with camostate + L-364,718. The pancreas weights and the concentrations of deoxyribonucleic acid and ribonucleic acid in the pancreas of rats treated with L-364,718 alone were significantly lower than values in control rats. These data indicate that camostate-induced pancreas growth in rats appears to be dependent on the actions of endogenous cholecystokinin and that cholecystokinin may play a role in the maintenance of pancreatic growth in normal rats.
Wisner
J R
JR
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
McLaughlin
R E
RE
Rich
K A
KA
Ozawa
S
S
Renner
I G
IG
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D020109:Devazepide; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology*; D006984:Hypertrophy / Q000139:chemically induced; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001570:Benzodiazepinones; D004952:Esters; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D016670:Gabexate; D002766:Cholecystokinin; D020109:Devazepide