Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A-receptor-deficient rats

Jpn J Pharmacol. 1999 Dec;81(4):339-45. doi: 10.1254/jjp.81.339.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allylglycine / analogs & derivatives
  • Allylglycine / pharmacology
  • Animals
  • Benzamidines / pharmacology
  • Bicarbonates / metabolism*
  • Blotting, Northern
  • Body Weight / drug effects
  • Cholecystokinin / metabolism
  • Eating / drug effects
  • Esters
  • Gabexate* / analogs & derivatives*
  • Gene Expression Regulation / genetics
  • Guanidines / pharmacology
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Pancreatic Juice / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Receptor, Cholecystokinin A
  • Receptors, Cholecystokinin / deficiency
  • Receptors, Cholecystokinin / genetics*
  • Secretin / biosynthesis*
  • Secretin / genetics
  • Trypsin Inhibitor, Kunitz Soybean / pharmacology
  • Trypsin Inhibitors / pharmacology*

Substances

  • Benzamidines
  • Bicarbonates
  • Esters
  • Guanidines
  • RNA, Messenger
  • Receptor, Cholecystokinin A
  • Receptors, Cholecystokinin
  • Trypsin Inhibitors
  • ethyl N-allyl-N-(2-methyl-3-(4-(4-amidinophenoxycarbonyl)phenyl)propenoyl)aminoacetate methanesulfonate
  • camostat
  • Allylglycine
  • Secretin
  • Gabexate
  • Cholecystokinin
  • Trypsin Inhibitor, Kunitz Soybean