Curr Opin Gastroenterol. 2011 Oct;27(6):536-42. doi: 10.1097/MOG.0b013e32834bd53f.
The review summarizes the past year's literature regarding the regulation of gastric exocrine and endocrine secretion, both basic science and clinical.
Gastric acid secretion is an elaborate and dynamic process that is regulated by neural (efferent and afferent), hormonal (e.g. gastrin), and paracrine (e.g. histamine, ghrelin, somatostatin) pathways as well as mechanical (e.g. distension) and chemical (e.g. amino acids) stimuli. Secretion of hydrochloric acid (HCl) by parietal cells involves translocation of HK-ATPase-containing cytoplasmic tubulovesicles to the apical membrane with subsequent electroneutral transport of hydronium ions in exchange for potassium. The main apical potassium channel is KCNQ1 which, when activated, assembles with its β-subunit KCNE2 to function as a constitutively open, voltage-insensitive, and acid-resistant luminal potassium channel. Proton pump inhibitors block acid secretion by covalently binding to cysteine residues accessible from the luminal surface of the HK-ATPase. Potassium-competitive ATPase blockers (P-CABs) act by competing for K on the luminal surface of HK-ATPase. As they are acid-stable and do not require acid-dependent activation, P-CABs hold promise for rapid and prolonged inhibition of acid secretion.
We continue to make progress in our understanding of the physiologic regulation of gastric acid secretion. A better understanding of the pathways and mechanisms regulating acid secretion should lead to improved management of patients with acid-induced disorders.
本文总结了过去一年有关胃外分泌和内分泌分泌的基础科学和临床研究的文献。
胃酸分泌是一个复杂而动态的过程，受神经（传出和传入）、激素（如胃泌素）和旁分泌（如组胺、胃饥饿素、生长抑素）以及机械（如扩张）和化学（如氨基酸）刺激的调节。壁细胞分泌盐酸（HCl）涉及 HK-ATPase 含有的细胞质小管泡向顶端膜的易位，随后通过电中性转运氢离子以交换钾离子。主要的顶端钾通道是 KCNQ1，当被激活时，与β亚基 KCNE2 组装形成一个组成型开放、电压不敏感且耐酸的腔钾通道。质子泵抑制剂通过与 HK-ATPase 从腔表面可及的半胱氨酸残基共价结合来抑制酸分泌。钾竞争性 ATP 酶抑制剂（P-CABs）通过在 HK-ATPase 的腔表面与 K 竞争而起作用。由于它们是酸稳定的，并且不需要酸依赖性激活，因此 P-CAB 有望快速和持久地抑制酸分泌。
我们在理解胃酸分泌的生理调节方面继续取得进展。更好地了解调节酸分泌的途径和机制应该会导致改善酸诱导疾病患者的管理。
