Metabolism of the 1-13 sequence of gastrin 17 in humans and failure to influence acid secretion.
The metabolism and action on basal and gastrin 17 (G-17)-stimulated acid secretion of the N-terminal 1-13 sequence of G-17 was studied in human volunteers. Basal acid secretion was not changed by infusion of 1-13 G-17 in doses of 75-1000 pmol X kg-1 X h-1 which gave plasma concentrations of N-terminal G-17 immunoreactivity of 150-2020 pmol X L-1. In addition the acid response to G-17 in a dose that stimulated about 50% maximal acid output was not influenced by 1-13 G-17 (75 and 1000 pmol X kg-1 X h-1). The mean half-time for disappearance of N-terminal immunoreactivity after stopping infusion of 1-13 G-17 was 9.8 +/- 0.5 min. Gel filtration indicated a single peak of N-terminal immunoreactivity in plasma during infusion of 1-13 G-17. Ion exchange chromatography on diethylaminoethyl cellulose, however, revealed two peaks of immunoreactivity. One corresponded to 1-13 G-17, the other eluted earlier. In samples taken after stopping the infusion, the variant predominated. On high-pressure liquid chromatography the variant was resolved into a major component, which had a retention time less than 1-13 G-17, and two minor components. The variants were not produced by incubation of 1-13 G-17 with plasma in vitro. It is concluded that 1-13 G-17 is converted in the circulation to new forms with longer half-lives. Because plasma enzymes cannot account for the formation of these variants, it is possible that enzymes present on cell walls, for example, on capillaries, may be responsible.
D000328:Adult; D000595:Amino Acid Sequence; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects; D005755:Gastrins / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D010443:Peptide Chain Termination, Translational; D011863:Radioimmunoassay
D005755:Gastrins; D007457:Iodine Radioisotopes; C013550:gastrin 17