Control of preprogastrin messenger RNA translation by gastric acid in the rat

Background & Aims: Plasma gastrin and tissue preprogastrin messenger RNA (mRNA) increase in rats treated with the proton pump inhibitor omeprazole, but changes in mRNA alone cannot account for calculated changes in gastrin synthesis. The possibility that there is control of preprogastrin mRNA translation rates was investigated. Methods: Preprogastrin mRNA translation was assessed by incorporation of [H-3]tyrosine into progastrin in rat antral mucosa in vitro at 22 degrees C; preprogastrin mRNA was determined by Northern blot analysis. Results: During incubation, incorporation of [H-3]tyrosine into progastrin was linear up to 4 hours, and preprogastrin mRNA was unchanged. Fasting (24 hours) decreased plasma gastrin levels by 75% and progastrin translation by 40%, but preprogastrin mRNA was unchanged. Conversely, omeprazole increased plasma gastrin levels 8-fold, preprogastrin mRNA 2-3-fold, and progastrin translation 6-fold. In a cell-free translation system, preprogastrin was increased in samples from omeprazole-treated rats in direct proportion to the increase in preprogastrin mRNA abundance. Conclusions: Stimulation of gastrin cells by achlorhydria or inhibition by fasting lead, respectively, to increased and decreased preprogastrin translation rates that are more pronounced than changes in mRNA abundance. Therefore, luminal acid controls preprogastrin mRNA translation independently of changes in mRNA abundance or gastrin release.