Gastric H,K-ATPase as a drug target
Gastric H,K-ATPase as a drug target
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DOI：
10.1007/s10620-005-9042-8
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发表时间：
2006-05-01
影响因子：
3.1
通讯作者：
Sachs, George
中科院分区：
文献类型：
--
作者：
Shin, Jai Moo;Sachs, George
Gastric acid is secreted by parietal cells in the stomach. These have two known acid stimulatory receptors, the H2 receptor and the muscarinic M3 receptor. Gastrin, the major endocrine activator of acid secretion, exerts its action via release of histamine from the ECL cell, as does pituitary adenylate cyclase activating peptide (PACAP), a neural mediator of activation of acid secretion. Antagonists of the former two stimulants inhibit gastric acid secretion. Cholinergic receptor antagonists have many side effects and are relatively weak inhibitors at therapeutic doses compared to H2 receptor antagonists. These drugs were widely developed in the 1970s and 1980s and became the first really useful medications for healing of peptic ulcers. However, although good for healing peptic ulcers, they were less effective for treatment of erosive esophagitis. Moreover, tolerance was found, reducing their efficacy by∼ 50% after∼ 5–7 days of treatment. They were effective in suppressing nighttime acidity but less so against daytime acidity.A new target, gastric H, K-ATPase, the transporter catalyzing the final step of acid secretion, supplanted the H2 receptor antagonists in the 1990s. The first class of drug to be used clinically is the proton pump inhibitor (PPI) class. PPIs covalently bind to gastric H, K-ATPase under acidic conditions and inhibit enzyme activity. A second class of drugs is under development, defined as acid pump antagonists (APAs),
