A novel effect of bismuth ions - Selective inhibition of the biological activity of glycine-extended gastrin

Pannequin, J; Kovac, S; Tantiongco, JP; Norton, RS; Shulkes, A; Barnham, KJ; Baldwin, GS

Author(s): Pannequin, J; Kovac, S; Tantiongco, JP; Norton, RS; Shulkes, A; Barnham, KJ; Baldwin, GS;
Details: Publication Year 2004-01-23,Volume 279,Issue #4,Page 2453-2460
Journal Title: JOURNAL OF BIOLOGICAL CHEMISTRY
Publication Type: Journal Article
Abstract: Although bismuth salts have been used for over two centuries for the treatment of various gastrointestinal disorders, the mechanism of their therapeutic action remains controversial. Because gastrins bind two trivalent ferric ions with high affinity, and because ferric ions are essential for the biological activity of glycine-extended gastrin 17, we have investigated the hypothesis that trivalent bismuth ions influence the biological activity of gastrins. Binding of bismuth ions to gastrins was measured by fluorescence quenching and NMR spectroscopy. The effects of bismuth ions on gastrin-stimulated biological activities were measured in inositol phosphate, cell proliferation, and cell migration assays. Fluorescence quenching experiments indicated that both glycine-extended and amidated gastrin 17 bound two bismuth ions. The NMR spectral changes observed on addition of bismuth ions revealed that Glu-7 acted as a ligand at the first bismuth ion binding site. In the presence of bismuth ions the ability of glycine-extended gastrin 17 to stimulate inositol phosphate production, cell proliferation, and cell migration was markedly reduced. In contrast, bismuth ions had little effect on the affinity of the CCK-2 receptor for amidated gastrin 17, or on the stimulation of inositol phosphate production by amidated gastrin 17. We conclude that bismuth ions may act, at least in part, by blocking the effects of glycine-extended gastrin 17 on cell proliferation and cell migration in the gastrointestinal tract. This is the first report of a specific inhibitory effect of bismuth ions on the action of a gastrointestinal hormone.
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Keywords: HELICOBACTER-PYLORI ERADICATION; COLON-CANCER CELLS; GROWTH-FACTOR; TRIPLE THERAPIES; TRANSGENIC MICE; FERRIC IONS; CRYPT FOCI; BINDING; PROGASTRIN; ACID
Publisher's Version: https://doi.org/10.1074/jbc.M309806200
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2004-01-23 12:00:00