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Depletion of enterochromaffin-like cell histamine increases histidine decarboxylase and chromogranin A mRNA levels in rat stomach by a gastrin-independent mechanism.

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Author

  • K Andersson
  • Elisabeth Lindström
  • D Chen
  • H J Monstein
  • Åke Boketoft
  • Rolf Håkanson

Summary, in English

BACKGROUND: Gastrin activates histidine decarboxylase (HDC) and increases HDC and chromogranin A (CGA) mRNA levels in histamine-producing enterochromaffin-like (ECL) cells in the rat stomach. We have studied how histamine depletion by subcutaneous infusion of the HDC inhibitor alpha-fluoromethyl-histidine (alpha-FMH) affects how ECL cells respond to hypergastrinemia in terms of HDC and CGA mRNA levels. METHODS: In one experiment rats received alpha-FMH for 24 h. In another experiment rats received alpha-FMH, omeprazole (perorally), or a combination of the two drugs for 10 days. In a third experiment antrectomized rats were treated with alpha-FMH for 48 h. The circulating gastrin level, oxyntic mucosal histamine concentration, HDC activity, and HDC and CGA mRNA levels were determined. RESULTS: alpha-FMH for 24 h increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. alpha-FMH for 10 days increased the serum gastrin concentration twofold. alpha-FMH + omeprazole resulted in the same serum gastrin concentration as after omeprazole alone (eightfold increase). HDC mRNA levels were higher after alpha-FMH + omeprazole than after omeprazole alone. alpha-FMH alone induced an HDC mRNA level that was similar in magnitude to that observed after omeprazole, although the serum gastrin concentration after alpha-FMH was much lower. In antrectomized rats alpha-FMH increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. CONCLUSION: ECL-cell histamine depletion will increase mRNA levels for HDC and CGA by a gastrin-independent mechanism, possibly involving abolished histamine autofeedback inhibition.

Department/s

Publishing year

1996

Language

English

Pages

65-959

Publication/Series

Scandinavian Journal of Gastroenterology

Volume

31

Issue

10

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Gastroenterology and Hepatology

Status

Published

Research group

  • Drug Target Discovery

ISBN/ISSN/Other

  • ISSN: 1502-7708