Bismuth ions inhibit the biological activity of non-amidated gastrins in vivo.
Bismuth ions inhibit the biological activity of non-amidated gastrins in vivo.
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DOI：
10.1016/j.bcp.2011.11.030
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发表时间：
2012-02-15
影响因子：
5.8
通讯作者：
Baldwin, Graham S.
中科院分区：
文献类型：
--
作者：
Kovac, Suzana;Loh, Su-Wen;Lachal, Shamilah;Shulkes, Arthur;Baldwin, Graham S.
肽激素胃泌素以高亲和力结合两个铁离子，并且铁结合对于非酰胺化胃泌素的体外和体内生物活性是必需的。Bi 3+离子也与甘氨酸延伸的胃泌素17（Ggly）结合，但在体外抑制Ggly诱导的胃肠道细胞系的细胞增殖和迁移。本研究的目的首先是建立Bi 3+离子抑制Fe 3+离子与Ggly结合的机制，其次是测试Bi 3+离子对体内非酰胺化胃泌素活性的影响。用紫外光谱法研究了Bi ~（3+）、Fe ~（3+）与甘氨酸的相互作用。在三种动物模型中测量Bi 3+离子对结直肠粘膜增殖的影响。在体外Bi 3+离子的存在下，Fe 3+离子对Ggly的亲和力大幅降低;数据更好地拟合混合，而不是竞争性抑制模型。在仅用Ggly处理的大鼠中，直肠粘膜的增殖增加了318%，但在接受口服铋加Ggly的动物中，增殖降低至对照值（p < 0.001）。过表达Ggly或前胃泌素的小鼠的结肠粘膜中的增殖显著大于野生型小鼠，但在接受口服铋的动物中不大于对照（p < 0.01）。因此，在Bi 3+离子存在下Fe 3+离子与Ggly和前胃泌素结合的减少是口服铋在体内阻断非酰胺化胃泌素的生物活性的能力的可能解释。
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. Bi3+ 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 Bi3+ ions inhibit the binding of Fe3+ ions to Ggly, and secondly, to test the effect of Bi3+ ions on the activity of non-amidated gastrins in vivo. The interaction between Bi3+ ions, Fe3+ ions and Ggly was investigated by ultraviolet spectroscopy. The effect of Bi3+ ions on colorectal mucosal proliferation was measured in three animal models. In vitro in the presence of Bi3+ ions the affinity of Fe3+ 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 Fe3+ ions to Ggly and progastrin in the presence of Bi3+ ions is a likely explanation for the ability of oral bismuth to block the biological activity of non-amidated gastrins in vivo.
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影响因子：
4
作者：
Pannequin, J;Tantiongco, JP;Baldwin, GS
通讯作者：
Baldwin, GS
DOI：
10.1016/j.bbrc.2010.12.117
发表时间：
2011-01-28
影响因子：
3.1
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通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
Koh, TJ;Dockray, GJ;Wang, TC
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Wang, TC