Bismuth ions inhibit the biological activity of non-amidated gastrins in vivo

作者：Kovac Suzana; Loh Su Wen; Lachal Shamilah; Shulkes Arthur; Baldwin Graham S^*

来源：Biochemical Pharmacology, 2012, 83(4): 524-530.

DOI：10.1016/j.bcp.2011.11.030

• Bismuth ions
• Colorectal mucosa
• Ferric ions
• Glycine-extended gastrin
• Proliferation
• Progastrin

The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated gastrins in vitro and in vivo. Bi(3+) ions also bind to glycine-extended gastrin17 (Ggly), but inhibit Ggly-induced cell proliferation and migration in gastrointestinal cell lines in vitro. The aims of the present study were firstly, to establish the mechanism by which Bi(3+) ions inhibit the binding of Fe(3+) ions to Ggly, and secondly, to test the effect of Bi(3+) ions on the activity of non-amidated gastrins in vivo. The interaction between Bi(3+) ions, Fe(3+) ions and Ggly was investigated by ultraviolet spectroscopy. The effect of Bi(3+) ions on colorectal mucosal proliferation was measured in three animal models. In vitro in the presence of Bi(3+) ions the affinity of Fe(3+) ions for Ggly was substantially reduced; the data was better fitted by a mixed, rather than a competitive, inhibition model. In rats treated with Ggly alone proliferation in the rectal mucosa was increased by 318%, but was reduced to control values (p < 0.001) in animals receiving oral bismuth plus Ggly. Proliferation in the colonic mucosa of mice overexpressing Ggly or progastrin was significantly greater than in wild-type mice, but was no greater than control (p < 0.01) in animals receiving oral bismuth. Thus a reduction in the binding of Fe(3+) ions to Ggly and progastrin in the presence of Bi(3+) ions is a likely explanation for the ability of oral bismuth to block the biological activity of non-amidated gastrins in vivo.

• 出版日期2012-2-15