Failure of a potent cholecystokinin antagonist to protect against diet-induced pancreatitis in mice

G. Ohshio, A. Saluja, U. Leli, A. Sengupta, M. L. Steer

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The effects of a potent cholecystokinin (CCK) receptor antagonist, L-364,718, on two forms of experimental acute pancreatitis in mice were evaluated. The antagonist prevented the hyperamylasemia, pancreatic edema, and acinar cell vacuolization that followed administration of a supramaximally stimulating dose of the cholecystokinin analogue cerulein. In contrast, the same dose of L-364,718 (1 mg/kg/6 h) and an even higher dose (10 mg/kg/6 h) failed to prevent the hyperamylasemia, acinar cell necrosis, and mortality that followed administration of a choline-deficient ethionine-supplemented diet. These observations are at variance with those previously reported to follow administration of the relatively weak cholecystokinin antagonist proglumide (Niederau C et al. J Clin Invest 1986;78:1056-63). The observations reported in this communication suggest that cholecystokinin does not play an important role in diet-induced pancreatitis and that CCK receptor antagonists are unlikely to be of benefit in the treatment of clinical acute pancreatitis.

Original languageEnglish (US)
Pages (from-to)739-743
Number of pages5
JournalPancreas
Volume4
Issue number6
DOIs
StatePublished - Dec 1989
Externally publishedYes

Keywords

  • 718
  • Cerulein
  • Choline deficiency
  • Ethionine
  • Hyperamylasemia
  • L-364
  • Pancreatic edema
  • Proglumide

ASJC Scopus subject areas

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

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