GASTRIC ION CHANNELS: ISOLATION AND CHARACTERIZATION

胃离子通道：分离和表征

• 批准号: 6199686
• 负责人: John Peter GEIBEL
• 金额: $ 26.64万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6199686
• 关键词: acidity /alkalinity; apical membrane; basolateral membrane; gap junctions; gastric acid; genetically modified animals; hormone regulation /control mechanism; hydrogen potassium exchanging ATPase; laboratory mouse; laboratory rat; membrane channels; membrane transport proteins; protein structure function; secretion; tissue /cell culture

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.

胃是消化进入人体的食物的主要部位。胃消化这种食物的能力与以下因素有关：有足够的底物来控制胃酸分泌，胃腺的顶端和底外侧膜上有功能运输蛋白，以及胃表面有足够的含有碳酸氢盐的粘液，以防止胃酸释放对膜的侵蚀。离子的调控释放通常由神经元和激素调控途径控制。然而，控制酸释放的确切机制尚不清楚，以及排列在基底外侧和根尖膜上的运输蛋白的完整表征。最近在胃腺基底外膜上发现了二价阳离子受体，以及鉴定了一种根尖Na-H转运蛋白和一种表面细胞NBC蛋白复合物，这些都为酸分泌的调节提供了新的见解。使用完整表面制备的能力，结合分离的灌注的单个胃腺，为研究和模拟完整组织提供了重要的载体。这些转运体的调控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酸分泌的复杂问题非常重要。为了增加研究武器库，我们最近开发了转基因模型，可以直接操纵胃中与酸分泌相关的分泌和调节途径。本应用程序的目的是分类和表征顶端和基底外侧膜相关的酸碱转运蛋白，并确定新发现的二价阳离子受体在控制其活性中起什么作用。特别强调将给予新发现的顶端Na- h和基底侧Na/HCO3在腺体和表面细胞的准备。进一步的研究还将探讨间隙连接在调节酸分泌中的作用。这些研究将包括使用分离的灌注胃腺、表面细胞和转基因模型来详细研究控制酸分泌的蛋白质的重要性。转运蛋白和受体的表征和调控将增强我们对酸分泌调节的基本理解，并将在制定治疗胃相关疾病的新策略中发挥重要作用。