Diazepam binding inhibitor is a potent cholecystokinin-releasing peptide in the intestine

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

97 Scopus Citations
View graph of relations

Author(s)

  • Karl-Heinz Herzig
  • Ilona Schön
  • Kazuhiko Tatemoto
  • Yoshihide Ohe
  • Ulrich R. Fölsch
  • Chung Owyang

Detail(s)

Original languageEnglish
Pages (from-to)7927-7932
Journal / PublicationProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number15
Publication statusPublished - 23 Jul 1996
Externally publishedYes

Abstract

Pancreatic proteases in the duodenum inhibit the release of cholecystokinin (CCK) and thus exert feedback control of pancreatic exocrine secretion. Exclusion of proteases from the duodenum either by the diversion of bile-pancreatic juice or by the addition of protease inhibitors stimulates exocrine pancreatic secretion. The mechanism by which pancreatic proteases in the duodenum regulate CCK secretion is unknown. In this study, we isolated a trypsin-sensitive peptide that is secreted intraduodenally, releases CCK, and stimulates pancreatic enzyme secretion in rats. This peptide was found to be identical to the porcine diazepam binding inhibitor by peptide sequencing and mass spectrometry analysis. Intraduodenal infusion of 200 ng of synthetic porcine diazepam binding inhibitor1-86 in rats significantly stimulated pancreatic amylase output. Infusion of the CCK antagonist MK-329 completely blocked the diazepam binding inhibitor-stimulated amylase secretion. Similarly, diazepam binding inhibitor33-50 also stimulated CCK release and pancreatic secretion in a dose-dependent manner although it was 100 times less potent than the whole peptide. Using a perfusion system containing isolated mucosal cells from the proximal intestine of rats, porcine diazepam binding inhibitor (10-9-10-12 M) dose dependently stimulated CCK secretion. In separate studies, it was demonstrated that luminal secretion of the diazepam binding inhibitor immunoreactivity (7.5 x 10-11 M) could be detected in rat's intestinal washing following the diversion of bile- pancreatic juice. The secretion of this peptide was inhibited by atropine. In conclusion, we have isolated and characterized a CCK-releasing peptide that has a sequence identical to the porcine diazepam binding inhibitor from pig intestinal mucosa and that stimulates CCK release when administered intraduodenally in rat. This peptide may mediate feedback regulation of pancreatic enzyme secretion.

Research Area(s)

  • exocrine pancreatic secretion, feedback control

Citation Format(s)

Diazepam binding inhibitor is a potent cholecystokinin-releasing peptide in the intestine. / Herzig, Karl-Heinz; Schön, Ilona; Tatemoto, Kazuhiko et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 15, 23.07.1996, p. 7927-7932.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review