Nagaya H, Satoh H
Biology Research Laboratories, Takeda Chemical Industries Ltd.
Nihon Rinsho. 1992 Jan;50(1):26-32.
Proton pump inhibitors are classified into two distinct types, and the mechanisms are reviewed. Substituted benzimidazole such as omeprazole and lansorrazole, inhibit (H+ + K+)-ATPase by reacting with SH groups of enzyme after the drugs are transformed into their active forms in the acidic environment of the intracellular canaliculi of parietal cells. This type of enzyme inhibition results in potent and long-lasting inhibition of gastric acid secretion. On the other hand, substituted imidazo pyridines, such as SCH 28080, inhibit (H+ + K+)-ATPase by competing with K+. This inhibition is reversible and the antisecretory effect is short-lived. Recent studies on DNA cloning and sequencing for (H+ + K+)-ATPase have led to a better understanding of enzyme structure and also the sites of action of the proton pump inhibitors.
质子泵抑制剂分为两种不同类型，并对其作用机制进行了综述。诸如奥美拉唑和兰索拉唑等取代苯并咪唑类药物，在壁细胞内小管的酸性环境中转化为活性形式后，通过与酶的巯基反应来抑制（H⁺+K⁺）-ATP酶。这种类型的酶抑制作用导致胃酸分泌受到强效且持久的抑制。另一方面，诸如SCH 28080等取代咪唑吡啶类药物，通过与K⁺竞争来抑制（H⁺+K⁺）-ATP酶。这种抑制作用是可逆的，且抗分泌作用是短暂的。最近关于（H⁺+K⁺）-ATP酶的DNA克隆和测序研究，使得人们对酶的结构以及质子泵抑制剂的作用位点有了更好的理解。
