Inhibition of the alpha-amidation of gastrin: effects on gastric acid secretion.
Inhibition of the alpha-amidation of gastrin: effects on gastric acid secretion.
复制标题
抑制胃泌素的α-酰胺化：对胃酸分泌的影响。
DOI：
10.1152/ajpgi.1990.258.5.g810
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Yamada,T
中科院分区：
文献类型：
--
作者：
Dickinson,CJ;Marino,L;Yamada,T
Formation of biologically active amidated gastrin from glycine-extended progastrin processing intermediates (G-Gly) is achieved via the action of peptidyl-glycyl alpha-amidating monooxygenase. Since this enzyme requires copper for optimal activity, we examined the effects of a known copper chelator, diethyldithiocarbamate (DDC), on gastrin posttranslational processing and gastric acid secretion in vivo. DDC (400 mg.kg-1.day-1 ip X 3 days) administered to male Sprague-Dawley rats decreased antral amidated gastrin content, but increased antral G-Gly content. The ratio of amidated gastrin to G-Gly, which reflects in situ amidating activity, was decreased in DDC-treated rats. In contrast, tissue amidating potential, assayed directly under optimal copper concentrations in vitro, was increased in the antrum and unchanged in the pituitary. DDC markedly increased both basal and gastrin-stimulated gastric acid outputs despite the presence of normal serum amidated gastrin levels. These results suggest that copper chelation with DDC inhibits amidating activity in situ but selectively increases antral amidating enzyme synthesis. The marked increase in acid secretion despite normal circulating amidated gastrin concentrations, combined with the enhanced secretory response to exogenously administered gastrin, suggests the possibility that gastrin receptors are upregulated by the events precipitated via DDC administration.
