Different Effects of Oral Administration of Synthetic Trypsin Inhibitor on the Pancreas Between Cholecystokinin-A Receptor Gene Knockout Mice and Wild Type Mice

[摘要] References(23)Cited-By(6)The synthetic trypsin inhibitor camostat has been used for the treatment of acute and chronic pancreatitis in Japan based on the evidences obtained from a rat experimental model. However, rats differ from other rodents and from humans in terms of lacking a gallbladder and no response of pancreatic bicarbonate secretion to cholecystokinin (CCK). In the present study, we determined whether oral administration of camostat showed a trophic effect in mice as observed in rats and whether the trophic effect, if substantial, was mediated via the CCK-A receptor, using CCK-A receptor gene targeting mice. The chow containing 0.1% camostat was fed to 8-month-old mice. Three- and seven-day treatments with camostat did not affect pancreatic wet weight in CCK-A receptor (+/−) mice. After 14-day treatment, the ratio of pancreatic wet weight/body weight was significantly lower in CCK-A receptor (−/−) than (+/+) mice. The protein and chymotrypsin contents were lower and amylase content was higher in CCK-A receptor (−/−) mice, compared to (+/+) mice. No pathological findings were observed by histological examination. Camostat has a trophic effect on the pancreas in mice and this effect is mediated via the CCK-A receptor, but is less potent than in rats.

[学科分类] 药理学

[关键词] Cholecystokinin (CCK);CCK-A receptor;Pancreas;Trypsin inhibitor