Modulation of posttranslational processing of gastrin precursor in dogs

A. Varro, J. Nemeth, J. Bridson, J. Lonovics, G. J. Dockray

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The precursor of the acid-stimulating hormone gastrin is processed in pyloric antral gastrin cells by steps involving sulfation, phosphorylation, cleavage, and amidation. We describe here changes in posttranslational processing in dogs with a surgically excluded antrum; in the preparation we used there was an intact pylorus but antral mucosa was excluded from the normal influence of the luminal contents. Three to five months after the operation, basal plasma gastrin increased from 30.1 ± 4.0 to 66.1 ± 16.1 pmol/l, and concentrations of gastrin in the excluded mucosa were 9.23 ± 1.75 compared with 3.2 ± 0.56 nmol/g in control antral mucosa. Calculations based on the metabolic clearance rate and plasma and tissue gastrin concentrations suggest two-fold lower fractional release rates from the excluded G-cells compared with normal G-cells. Radioimmunoassay of tissue extracts using antisera specific for the extreme COOH-terminus of progastrin, for glycine-extended G-17, and for the COOH-terminus of G-17, combined with gel filtration and ion exchange chromatography, indicated normal endopeptidase cleavage of progastrin. However there was significantly reduced phosphorylation of the COOH-terminal tryptic fragment of progastrin, and there was also decreased conversion of Gly-extended intermediates to the biologically active COOH-terminally amidated forms of gastrin. Thus, in spite of hypergastrinaemia, the excluded antral mucosa showed evidence of decreased secretory rates associated with decreased progastrin phosphorylation and amidating enzyme activity. The results suggest that contact of antral mucosa with the luminal contents is able to modulate the posttranslational processing of progastrin and so determine the production of biologically active hormone.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume258
Issue number6 21-6
Publication statusPublished - 1990

Fingerprint

Gastrins
Mucous Membrane
Gastrin-Secreting Cells
Dogs
Phosphorylation
Secretory Rate
Hormones
Metabolic Clearance Rate
Endopeptidases
Tissue Extracts
Pylorus
Ion Exchange Chromatography
Glycine
Radioimmunoassay
Gel Chromatography
Immune Sera
big gastrin
Antral
Acids
Enzymes

Keywords

  • amidation, hypergastrinemia
  • biosynthesis
  • cleavage
  • gastrin
  • phosphorylation

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

Modulation of posttranslational processing of gastrin precursor in dogs. / Varro, A.; Nemeth, J.; Bridson, J.; Lonovics, J.; Dockray, G. J.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 258, No. 6 21-6, 1990.

Research output: Contribution to journalArticle

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