Effects of a new cholecystokinin antagonist, TS-941, on experimental acute pancreatitis in rats

Youxue Wang, Satoru Naruse, Motoji Kitagawa, Hiroshi Ishiguro, Yasuyuki Nakae, Toshiyuki Yoshikawa, Tetsuo Hayakawa

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The effects of a new benzodiazepine-derivative, cholecystokinin receptor antagonist, TS-941, on experimental acute pancreatitis were studied in rats. Hemorrhagic pancreatitis was induced by an infusion of a mixture of trypsin and taurocholate into the pancreatic duct. Edematous pancreatitis was induced by intraperitoneal injection of 40 μg/kg body weight of cerulein at 0 and 1 h after the start of the experiment. TS-941 (3 mg/kg) was injected subcutaneously immediately and 3 h after the induction of pancreatitis. In trypsin-taurocholate-induced pancreatitis, TS-941, with or without the synthetic trypsin inhibitor ONO-3403, had no beneficial effects on the survival rate, pancreatic wet weight, and serum pancreatic enzymes. In cerulein-induced pancreatitis, the treatment with TS-941 significantly reduced the increases of pancreatic wet weight and serum amylase and lipase. Plasma trypsinogen activation peptide (TAP) significantly rose 1 h after the first injection of cerulein. TS-941 inhibited the liberation of TAP in cerulein-induced pancreatitis. These results show that TS-941 is effective for prevention of cerulein-induced edematous pancreatitis. ONO-3403 has beneficial effects on trypsin-taurocholate-induced hemorrhagic pancreatitis, but the combination of TS-941 and ONO-3403 has no additive effect.

Original languageEnglish (US)
Pages (from-to)289-294
Number of pages6
JournalPancreas
Volume17
Issue number3
DOIs
StatePublished - Oct 1998

Keywords

  • Cholecystokinin receptor antagonist
  • Experimental pancreatitis
  • Trypsinogen activation peptide (TAP)
  • α macroglobulin trypsin complex

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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    Wang, Y., Naruse, S., Kitagawa, M., Ishiguro, H., Nakae, Y., Yoshikawa, T., & Hayakawa, T. (1998). Effects of a new cholecystokinin antagonist, TS-941, on experimental acute pancreatitis in rats. Pancreas, 17(3), 289-294. https://doi.org/10.1097/00006676-199810000-00011