Different effects of oral administration of synthetic trypsin inhibitor on the pancreas between cholecystokinin-A receptor gene knockout mice and wild type mice

Jpn J Pharmacol. 2002 Jul;89(3):290-5. doi: 10.1254/jjp.89.290.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Female
  • Gabexate / analogs & derivatives*
  • Gabexate / pharmacology
  • Male
  • Mice
  • Mice, Knockout
  • Pancreas / cytology
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Plant Proteins / pharmacology*
  • Receptor, Cholecystokinin A
  • Receptors, Cholecystokinin / deficiency*
  • Receptors, Cholecystokinin / genetics
  • Receptors, Cholecystokinin / metabolism
  • Trypsin / metabolism
  • Trypsin Inhibitors
  • alpha-Amylases / antagonists & inhibitors

Substances

  • Plant Proteins
  • Receptor, Cholecystokinin A
  • Receptors, Cholecystokinin
  • Trypsin Inhibitors
  • camostat
  • Gabexate
  • alpha-Amylases
  • Trypsin