泮托拉唑
兰索拉唑
雷贝拉唑
奥美拉唑
埃索美拉唑
质子抑制剂泵
胃酸
壁细胞
医学
H(+)-K(+)-交换ATP酶
药理学
半胱氨酸
化学
分泌物
生物化学
ATP酶
内科学
酶
作者
George Sachs,Jai Moo Shin,Vijaya S. Pratha,Daniel L. Hogan
出处
期刊:PubMed
日期:2003-03-01
卷期号:39 Suppl A: 11-4
被引量:9
摘要
Insight has been gained into the relationship between the structure of proton pump inhibitors (PPIs), their binding, and their suppression of acid secretion. PPIs accumulate in the acidic space of the secreting parietal cell, where then their active forms create disulfide bonds with key cysteines of the H(+), K(+)-ATPase. Studies in humans on the half-lives of recovery of acid secretion have found that while lansoprazole showed a half-life of less than 15 h, and both omeprazole and rabeprazole showed one of less than 30 h, for pantoprazole the half-life was approximately 46 h. This difference in duration of inhibition with PPIs may be related to variations in proton pump inhibitor dwell time. A study in rats suggests that the recovery of gastric pump activity after treatment with omeprazole, esomeprazole, lansoprazole and rabeprazole is likely due to both reversal of binding by disulfide-reducing agents and to pump synthesis. However, for pantoprazole, reversal of acid inhibition is probably due mainly to de novo pump synthesis and not loss of binding. This profile is likely related to the unique binding of pantoprazole to cysteine 822, a binding site which is buried deep within the membrane domain of the pump and may therefore be inaccessible to reducing agents. Although clinical data supporting these findings are limited, prolonged binding of pantoprazole may confer a longer duration of action in comparison with other PPIs.
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