Y. Ogura, S. Matsuda, M. Itho
Jan 18, 2002
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Journal
World Journal of Surgery
Abstract
We evaluated the cholecystokinin (CCK)receptor antagonist loxiglumide (CR1505) for a possible inhibitoryeffect on biliary carcinogenesis in a hamster model. Experimental groupI underwent cholecystoduodenostomy and ligation of the distal end ofthe common bile duct, after which the animals were injected withN-nitrosobis(2-oxopropyl)amine (BOP) alone. Group II, afterthe same surgical procedure as in group I, were given injections of BOPand then given loxiglumide in their diet. The sham-operated groupunderwent simple laparotomy and then were given injections of BOP.Loxiglumide significantly inhibited BOP carcinogenicity in thegallbladder and extrahepatic bile duct but not in the intrahepatic bileducts or pancreas. Autoradiography showed that loxiglumidesignificantly suppressed 125I-Bolton-Hanter (BH)-CCK-8binding to CCK receptors in the gallbladder and extrahepatic bile ductbut not in the liver or pancreas, and CCK binding to its receptors wasobserved in an area identified as cancer tissue. CCK receptorantagonists have an inhibitory effect on BOP carcinogenesis in theextrahepatic biliary tract, including the gallbladder and extrahepaticbile duct, of Syrian hamsters. The difference in the inhibitory effectof loxiglumide on biliary carcinogenesis in hamsters according to sitemay be due to differences in CCK receptors or the affinity ofloxiglumide for such biliary tract organs. A difference betweencarcinogenesis in the intrahepatic bile ducts and extrahepatic biliarytract may be another reason.