Increased tissue concentrations of the gastrin precursor in patients treated with omeprazole.
The main form of gastrin in antral mucosa, the amidated heptadecapeptide G17, is generated from an inactive precursor, progastrin, by steps involving endopeptidase cleavage and amidation. Gastrin cells are normally inhibited by gastric acid and in this study we have examined how suppression of acid by treatment with omeprazole for 6-8 weeks influences gastrin production in patients with oesophagitis. Plasma concentrations of total amidated gastrins in the fasting state increased from 18 to 43 pmol l-1; assays specific for G17-immunoreactivity indicated that the plasma concentrations of this form increased from 6 to 12 pmol l-1. In endoscopic biopsies of antral mucosa there was no change with omeprazole treatment in the concentrations of total amidated gastrins, or their immediate precursors, the Gly-extended gastrins. However, assays using an antibody that reacts with progastrin, together with size exclusion chromatography, indicated that tissue progastrin concentration increased 6-fold. The data suggest a modest net increase in gastrin production with omeprazole-treatment; because the ratio of tissue concentrations of total amidated gastrins to Gly-extended gastrins did not change, it would seem that the amidating capacity of the gastrin cell was maintained. However, the increase in progastrin concentrations suggests a relative failure of the initial steps of post-translational processing, and consequently that in certain circumstances endopeptidase cleavage of progastrin may be rate limiting.
Nemeth
J
J
Physiological Laboratory, University of Liverpool, UK.
Varro
A
A
Bridson
J
J
Walker
R
R
Dockray
G J
GJ
D000595:Amino Acid Sequence; D004941:Esophagitis / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009853:Omeprazole / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011706:Pyloric Antrum / Q000378:metabolism; D014018:Tissue Distribution
D005755:Gastrins; D010446:Peptide Fragments; D011498:Protein Precursors; C013706:big gastrin; D009853:Omeprazole