Takeuchi K
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Nihon Yakurigaku Zasshi. 1996 Dec;108(6):281-93. doi: 10.1254/fpj.108.6_281.
Bicarbonate secretion from the surface epithelial cells of the gastroduodenal mucosa is an active process depending upon the tissue metabolism and plays an important role as the first line of defense in mucosal protection in collaboration with the mucus gel. This secretion is regulated by humoral and neural factors as well as endogenous prostaglandins (PGs) and is considered to be intracellularly mediated by cyclic AMP in the duodenum and by cyclic GMP in the stomach. Ca2 also acts as an intracellular mediator in this process. This bicarbonate secretion is markedly increased in response to luminal acid, mediated by PGs and neural factors including capsaicin-sensitive sensory nerves, and the impairment of this response is involved in the pathogenesis of various duodenal ulcer models induced by cysteamine, nonsteroidal antiinflammatory drugs and stress. The mechanisms underlying the mucosal protection by HCO3 secretion is two fold; One is the direct neutralization of H + in the lumen, and the other is the establishment of a pH gradient across the mucus gel aided by the physico-chemical property of the mucus. However, the cellular mechanisms of HCO3 secretion, including the receptors, the mediators and the signal transduction pathway have been poorly understood. The establishment of a method for preparing isolated epithelial cells and the probe for HCO3 secretion in isolated cells is required to further elucidate the mechanism of HCO3 secretion.
胃十二指肠黏膜表面上皮细胞分泌碳酸氢盐是一个依赖组织代谢的活跃过程，并且在与黏液凝胶协同发挥黏膜保护的第一道防线作用中扮演重要角色。这种分泌受体液和神经因素以及内源性前列腺素（PGs）调节，在十二指肠中被认为由环磷酸腺苷（cAMP）介导，在胃中由环磷酸鸟苷（cGMP）介导。钙离子（Ca2+）在此过程中也作为细胞内介质发挥作用。这种碳酸氢盐分泌在受到腔内酸刺激时会显著增加，由PGs和包括辣椒素敏感感觉神经在内的神经因素介导，而这种反应的受损参与了由半胱胺、非甾体抗炎药和应激诱导的各种十二指肠溃疡模型的发病机制。通过分泌碳酸氢盐进行黏膜保护的机制有两个方面：一是直接中和腔内的氢离子（H+），另一个是借助黏液的物理化学性质在黏液凝胶上建立pH梯度。然而，碳酸氢盐分泌的细胞机制，包括受体、介质和信号转导途径，目前还了解甚少。需要建立一种制备分离上皮细胞的方法以及用于分离细胞中碳酸氢盐分泌的探针，以进一步阐明碳酸氢盐分泌的机制。
