Influence of cholecystokinin antagonist on the effects of cholecystokinin and bombesin on azaserine-induced lesions in rat pancreas

Gastroenterology. 1989 Feb;96(2 Pt 1):462-9. doi: 10.1016/0016-5085(89)91572-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azaserine / pharmacology*
  • Bombesin / pharmacology*
  • Cholecystokinin / antagonists & inhibitors
  • Cholecystokinin / blood
  • Cholecystokinin / pharmacology*
  • Glutamine / analogs & derivatives*
  • Male
  • Pancreas / pathology*
  • Proglumide / analogs & derivatives*
  • Proglumide / pharmacology
  • Rats
  • Rats, Inbred Strains


  • Glutamine
  • Azaserine
  • Cholecystokinin
  • Proglumide
  • lorglumide
  • Bombesin