Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A-receptor-deficient rats.
The effects of oral administration of two synthetic trypsin inhibitors (camostate and ONO-3403) and soybean trypsin inhibitor (SBTI) on cholecystokinin (CCK), secretin gene expression and pancreatic secretion were examined in CCK-A-receptor-deficient (OLETF) rats. The rats were fed chow containing 0.1% trypsin inhibitors for 7 days. To examine pancreatic secretion, the rats were prepared with cannulae to drain the bile and pancreatic juice separately, a duodenal cannula and an external jugular vein cannula. The animals were maintained in Bollman cages and the experiments were conducted 4 days after surgery. The levels of CCK mRNA were significantly increased by each treatment. The levels of secretin mRNA were significantly increased by camostate and SBTI, but not by ONO-3403. Bicarbonate secretion was significantly increased in rats treated with camostate and ONO-3403, but not SBTI, while protein secretion was not affected by any treatment. These observations suggest that increased bicarbonate secretion produced by synthetic trypsin inhibitors in CCK-A-receptor-deficient rats may not be due to secretin but due to ONO-3403 in the circulation.
Kawanami
T
T
Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Japan.
Suzuki
S
S
Yoshida
Y
Y
Kanai
S
S
Takata
Y
Y
Shimazoe
T
T
Watanabe
S
S
Funakoshi
A
A
Miyasaka
K
K
D000501:Allylglycine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D002766:Cholecystokinin / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D005786:Gene Expression Regulation / Q000235:genetics; D006146:Guanidines / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000172:deficiency / Q000235:genetics*; D012633:Secretin / Q000096:biosynthesis* / Q000235:genetics; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D001550:Benzamidines; D001639:Bicarbonates; D004952:Esters; D006146:Guanidines; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D014361:Trypsin Inhibitors; C100807:ethyl N-allyl-N-(2-methyl-3-(4-(4-amidinophenoxycarbonyl)phenyl)propenoyl)aminoacetate methanesulfonate; C034532:camostat; D000501:Allylglycine; D012633:Secretin; D016670:Gabexate; D002766:Cholecystokinin; D014360:Trypsin Inhibitor, Kunitz Soybean