GASTRIN BIOSYNTHESIS IN THE ANTRUM OF PATIENTS WITH PERNICIOUS-ANEMIA

Background & Aims: The gastrin precursor progastrin produces multiple alternative active products, but the pathways of posttranslational pro cessing in human antral mucosa have not yet been studied directly. The aim of this study was to investigate the biosynthetic relationships a nd release kinetics of newly synthesized progastrin-derived peptides i n the antrum of patients with pernicious anemia. Methods: Antral mucos al explants were incubated with [S-35]sulfate and [H-3]tyrosine to lab el progastrin and its derivatives, which were detected by online scint illation counting after immunoprecipitation and high-performance liqui d chromatography. Results: [S-35]- and [H-3]progastrin were detected w ithin 2.5 hours, and labeled G34Gly and G34 were readily detected afte r 5-hour incubation. pulse-chase studies indicated conversion of proga strin to G17 via G34Gly and G34. Secretion of newly synthesized G34, b ut not G34Gly, was routinely detected; G17Gly was present only in trac e quantities in cell extracts and media. In control samples, progastri n synthesis was about 10 times lower than in pernicious anemia samples , although the proportions of different labeled amidated gastrins afte r 5-hour incubation were similar. Conclusions: In the antrum of patien ts with pernicious anemia, Gly-gastrins, particularly G34Gly, are bios ynthetic intermediates and not major secretory products. Some G34 is s ecreted preferentially under basal conditions.