Different effects of oral administration of synthetic trypsin inhibitor on the pancreas between cholecystokinin-A receptor gene knockout mice and wild type mice.
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.
Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Japan. norisato@tmig.or.jp
Norikazu
N
Sato
Shinji
S
Suzuki
Setsuko
S
Kanai
Minoru
M
Ohta
Atsuo
A
Jimi
Tetsuo
T
Noda
Souichi
S
Takiguchi
Akihiro
A
Funakoshi
Kyoko
K
Miyasaka
D000284:Administration, Oral; D000818:Animals; D004952:Esters; D005260:Female; D016670:Gabexate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006146:Guanidines; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010940:Plant Proteins / Q000494:pharmacology*; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
D004952:Esters; D006146:Guanidines; D010940:Plant Proteins; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D014361:Trypsin Inhibitors; C034532:camostat; D016670:Gabexate; D000516:alpha-Amylases; D014357:Trypsin