Progastrin processing during antral G-cell hypersecretion in humans

Abstract

Using radioimmunoassays specific for essential processing sites of human progastrin in combination with chromatography before and after cleavage with trypsin and carboxypeptidase B, we have examined antrat biopsy specimens and serum from 10 hypergastrinemic patients with fundic atrophic gastritis and 7 normal control subjects. Four types of processing were studied: N-terminal proteolysis (at the N-terminus of component I, gastrin 34, and gastrin 17); C-terminal proteolysis (at the C-terminus of the amide donor, glycine93 in preprogastrin); α-carboxyamidation (of phenylalanine92); and O-sulfation (of tyrosine87). The results show that progastrin during permanent G-cell hypersecretion is less completely processed with respect to C-terminal proteolysis, α-amidation, and tyrosine-sulfation. In contrast, the degree of N-terminal proteolysis is normal. Thus, the processing of progastrin adjacent to the active site of gastrin is more restrictively controlled than N-terminal processing during G-cell hypersecretion associated with pernicious anemia.