Effects of cholecystokinin and bombesin on development of azaserine-induced pancreatic tumours in rats: modulation by the cholecystokinin receptor antagonist lorglumide.
Cholecystokinin and bombesin have been shown to promote pancreatic growth and development of azaserine-induced acidophilic atypical acinar cell nodules in rat pancreas after treatment for 16 weeks. Lorglumide, a specific cholecystokinin receptor antagonist, inhibited the stimulating effect of cholecystokinin, but not of bombesin. The present study was carried out to determine effects of cholecystokinin and bombesin, alone and in combination with lorglumide, on pancreatic growth and carcinogenesis after chronic treatment. The animals were killed 8 months after the start of treatment. Growth of the pancreas and the development of acidophilic atypical acinar cell nodules in exocrine pancreas was enhanced significantly by both cholecystokinin and bombesin, but the number of carcinomas was increased only by bombesin. Lorglumide inhibited the effects of cholecystokinin on both pancreatic growth and on the development of acidophilic nodules. The effects of bombesin on pancreatic growth and development of pancreatic lesions, except for adenomas, were not inhibited by lorglumide.
Meijers
M
M
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Appel
M J
MJ
van Garderen-Hoetmer
A
A
Lamers
C B
CB
Rovati
L C
LC
Jansen
J B
JB
Woutersen
R A
RA
D000818:Animals; D001377:Azaserine; D001839:Bombesin / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity*; D004357:Drug Synergism; D008297:Male; D010190:Pancreatic Neoplasms / Q000139:chemically induced*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D002273:Carcinogens; D011949:Receptors, Cholecystokinin; D001377:Azaserine; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide; D001839:Bombesin