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新型抗溃疡药物依罗替丁存在下胃硫黏液的合成与分泌

Synthesis and secretion of gastric sulfomucin in the presence of ebrotidine, a new antiulcer agent.

作者信息

Slomiany B L, Lopez R A, Slomiany A

机构信息

Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark 07103-2400.

出版信息

Biochem Int. 1992 Dec;28(4):665-74.

PMID:1482403
Abstract

The effect of a new antiulcer agent, ebrotidine, on the synthesis and secretion of gastric sulfomucin was investigated using mucosal segments incubated in the presence of [3H]proline, [3H]glucosamine and [35S]Na2SO4. The drug, while showing no discernible effect on the apomucin synthesis, evoked a dose-dependent increase in mucin glycosylation and sulfation, which at 100 microM ebrotidine, attained its maximum of 2.4 and 2.7-fold stimulation, respectively. The analysis of mucin secretory responses revealed that ebrotidine caused a concentration-dependent enhancement in sulfomucin secretion which attained its maximum increase of 3.3-fold at 100-120 microM ebrotidine. The sulfomucin elaborated in the presence of ebrotidine exhibited a higher content of a large molecular-weight mucus glycoprotein form, the assembly of which is intimately associated with the sulfation event. The results suggest that the ability of ebrotidine to enhance gastric sulfomucin synthesis and secretion may play an important role in the gastroprotective mechanism of action of this agent.

摘要

使用在[3H]脯氨酸、[3H]氨基葡萄糖和[35S]硫酸钠存在下孵育的黏膜片段,研究了一种新型抗溃疡药物依罗替丁对胃硫酸黏蛋白合成和分泌的影响。该药物对脱辅基黏蛋白合成无明显作用,但能引起黏蛋白糖基化和硫酸化的剂量依赖性增加,在100微摩尔依罗替丁时,分别达到最大刺激倍数2.4倍和2.7倍。对黏蛋白分泌反应的分析表明,依罗替丁可引起硫酸黏蛋白分泌的浓度依赖性增强,在100 - 120微摩尔依罗替丁时最大增加3.3倍。在依罗替丁存在下产生的硫酸黏蛋白表现出高分子量黏液糖蛋白形式的含量更高,其组装与硫酸化事件密切相关。结果表明,依罗替丁增强胃硫酸黏蛋白合成和分泌的能力可能在该药物的胃保护作用机制中起重要作用。

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