Influence of CCK antagonist L-364,718, pancreastatin (33-49) and a somatostatin analogue on camostate-induced rat pancreatic hypertrophy.
Since endogenous cholecystokinin (CCK) is released after oral administration of camostate, it has been suggested that camostate-induced pancreatic growth is mediated via circulating CCK. To test this concept, we investigated the effects of three potentially inhibitory substances on rat pancreatic hypertrophy caused by feeding of camostate over 2 weeks: (1) L-364,718, the novel specific highly potent nonpeptide CCK receptor antagonist, (2) octreotide (SMS 201-995), a potent long-lasting somatostatin analogue and (3) pancreastatin (33-49), the biologically active C-terminal fragment of the novel gastrointestinal peptide pancreastatin. Camostate feeding (200 mg/kg) once daily for 14 days induced a significant increase in pancreatic weight, total protein, trypsinogen and polyamine levels, whereas total amylase content was substantially diminished. Simultaneous oral or subcutaneous treatment with L-364,718 (0.3 mg/kg twice daily) completely suppressed all trophic effects of camostate. Octreotide (25 micrograms/kg twice daily s.c.) and pancreastatin (33-49) (10 micrograms/kg twice daily s.c.) did not change any trophic parameter. In case of octreotide it could be shown that two daily injections only partially suppressed elevated CCK levels. Pancreatic DNA and putrescine levels were slightly reduced in rats receiving the CCK antagonist alone. These results demonstrate that camostate-induced pancreatic hypertrophy in rats is caused by the release of endogenous CCK which may contribute to the maintenance of normal pancreatic DNA and putrescine concentrations.
Schmidt
W E
WE
Department of Medicine, Georg-August University of Göttingen, FRG.
Stöckmann
F
F
Choudhury
A R
AR
Wilms
H M
HM
Siegel
E G
EG
Nustede
R
R
Fölsch
U R
UR
Creutzfeldt
W
W
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D053379:Chromogranin A; D020109:Devazepide; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology; D006984:Hypertrophy; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D010179:Pancreas / Q000473:pathology*; D010187:Pancreatic Hormones / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001570:Benzodiazepinones; D053379:Chromogranin A; D004952:Esters; D006146:Guanidines; D010187:Pancreatic Hormones; D011480:Protease Inhibitors; C034532:camostat; C050836:pancreastatin; D016670:Gabexate; D002766:Cholecystokinin; D020109:Devazepide; D015282:Octreotide