Influence of cholecystokinin antagonist on the effects of cholecystokinin and bombesin on azaserine-induced lesions in rat pancreas.
Both cholecystokinin and bombesin have been shown to promote pancreatic carcinogenesis in the azaserine-rat model. The present study was undertaken to discriminate between the effects of cholecystokinin and bombesin and to establish the modulating properties of the specific cholecystokinin receptor antagonist CR-1409 on pancreatic carcinogenesis. After initiation with 30 mg/kg of azaserine, six groups of 15 Wistar rats were treated for 16 wk with cholecystokinin, bombesin, or gelatin (control), some in combination with CR-1409. Doses of cholecystokinin (2.5 micrograms/kg) and bombesin (10 micrograms/kg) were chosen that rendered approximately equal plasma cholecystokinin levels. Both cholecystokinin and bombesin were found to stimulate pancreatic growth, whereas CR-1409 only inhibited the growth-promoting effect of cholecystokinin significantly. Furthermore, both peptides stimulated the development of putative preneoplastic lesions, whereas CR-1409 only inhibited the effect of cholecystokinin significantly. It is concluded that (a) CR-1409 inhibits the promoting effect of cholecystokinin on pancreatic growth and azaserine-induced early pancreatic lesions and (b) the effects of bombesin cannot be fully ascribed to stimulation of the secretion of endogenous cholecystokinin.
Douglas
B R
BR
Department of Gastroenterology and Hepatology, University Hospital, Leiden, the Netherlands.
Woutersen
R A
RA
Jansen
J B
JB
de Jong
A J
AJ
Rovati
L C
LC
Lamers
C B
CB
D000818:Animals; D001377:Azaserine / Q000494:pharmacology*; D001839:Bombesin / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D005973:Glutamine / Q000031:analogs & derivatives*; D008297:Male; D010179:Pancreas / Q000473:pathology*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D005973:Glutamine; D001377:Azaserine; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide; D001839:Bombesin