A MICROSURGICAL INVESTIGATION OF GASTRIC ACID SECRETION

胃是消化进入体内的食物的主要部位。胃消化这种食物的能力与胃腺顶端和基底外侧膜有足够的底物用于控制酸分泌，以及胃腺表面有足够的含有碳酸氢盐的粘液以防止由于释放的酸而对膜的侵蚀有关。正常情况下，离子的调节释放由神经元和激素调节通路控制。然而，受控酸释放的确切机制尚不清楚，也不知道排列在基侧和根尖膜上的运输蛋白的完整特征。最近在胃腺基底外侧膜上发现了一个二价阳离子受体，并发现了一个顶端Na-H转运蛋白和一个表面细胞NBC蛋白复合体，这些都增加了对胃酸分泌调节的新见解。能够使用完整的表面准备，结合隔离的灌流的单个胃腺，为研究和模拟完整的组织提供了重要的载体。这些转运蛋白的调节和信号信息从一个细胞到另一个细胞的传递对于理解健康和疾病中复杂的酸分泌问题非常重要。为了增加研究的武器库，我们最近开发了转基因模型，将允许直接操纵与胃酸分泌相关的分泌和调节途径。本申请的目的是对顶端和基底侧膜相关的酸碱转运体进行分类和表征，并确定新发现的二价阳离子受体在控制其活性方面所起的作用。将特别强调新发现的顶端Na-H，以及腺体和表面细胞准备中的基侧Na/HCO3。其他研究还将探讨缝隙连接在调节胃酸分泌中的作用。这些研究将包括使用分离的灌流胃腺、表面细胞和转基因模型来详细研究控制胃酸分泌的蛋白质的重要性。转运蛋白和受体的特性和调控将增强我们对调节胃酸分泌的基本了解，并将在制定治疗人群中胃部相关疾病的新策略方面发挥重要作用。

The stomach acts as the primary site of digestion of food taken into the body. The ability of the stomach to digest this food is linked to having sufficient substrates for controlled acid secretion, and functional transport proteins at the apical and basolateral membrane of the gastric gland along with sufficient bicarbonate containing mucus at the surface of the stomach to prevent erosion of the membranes due to the released acid. The regulated release of ions is normally controlled by neuronal and hormonal regulatory pathways. However, the exact mechanisms of controlled acid release are not known, as well as a complete characterization of the transport proteins that line the basolateral and apical membranes. The recent discovery of a divalent cation receptor on the basolateral membrane of the gastric gland as well as the identification of an apical Na-H transport protein and a surface cell NBC protein complex have added addition insights into the regulation of acid secretion. The ability to use an intact surface preparation, in combination with the isolated perfused single gastric gland gives important vehicles for studying and modeling the intact tissues. The regulation of these transporters and the transfer of signal information from one cell to the other is of great importance in understanding the complex issues of acid secretion in health and disease. To add to the investigative arsenal we have recently developed transgenic models that will allow direct manipulation of the secretory and regulatory pathways associated with acid secretion in the stomach. The goal of the present application is to classify, and characterize the apical and basolateral membrane associated acid-base transporters and to determine what role the newly identified divalent cation receptor plays in controlling their activity. Special emphasis will be given to the newly identified apical Na-H, and the basolateral Na/HCO3 in the gland and surface cell preparations. Additional studies will also address the role of gap junctions in regulated acid secretion. These studies will include the use of isolated perfused gastric glands, surface cells, and transgenic models to study in detail the importance of the proteins which control acid secretion. The characterization and modulation of transport proteins and receptors will enhance our basic understanding of regulated acid secretion and will play an important role in developing new strategies for the treatment of gastric related illness in the population.