MICROSURGICAL INVESTIGATION OF GASTRIC ACID SECRETION

胃酸分泌的显微外科研究

• 批准号: 6311013
• 负责人: John Peter GEIBEL
• 金额: $ 9.33万
• 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 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6311013
• 关键词: acidity /alkalinity; apical membrane; calcium channel blockers; calcium flux; calcium ion; enzyme activity; fluorescent dye /probe; gastric acid; histamine receptor; hormone regulation /control mechanism; hydrogen potassium exchanging ATPase; inositol phosphates; laboratory rabbit; membrane transport proteins; microsurgery; potassium channel; protein kinase A; protein kinase C; second messengers; secretion; sodium ion; sodium potassium exchanging ATPase; tissue /cell culture

DESCRIPTION: (Adapted from investigator's abstract) It is well known that the stomach plays a critical role in the digestion of foodstuffs taken in by the body by generating a solution that contains 0.16N hydrochloric acid. This role is essential for the normal survival of the organism. The conductive movement of H+ ions across the apical membrane plays a key role in acid secretion. The coupling of the net efflux of H+ ions with the recycling of K+ ions allows us to maintain the continued acid flux that occurs during stimulated acid secretion. In addition to this movement one expects to observe a parallel efflux of chloride to aid in the generation of acid from the gland lumen. The stimulated loss of acid occurs when the H-K-ATPase is actively inserted into the apical membrane causing a proton efflux from cell to lumen of the gland. What happens to the cells of the gland during the non-stimulated state is completely unknown due to the previous inaccessibility to the apical surface of the intact gland. The key focus of this grant will be to use the various techniques that have been developed in our laboratory to access the apical surface of the intact gland and to examine the biophysics and regulation of acid secretion transcellularly, focusing on the changes that develop from the non-stimulated gland to the stimulated gland. We will use our findings to explain what changes are developing in the stomach during both hyper- and hypoacidic states and to examine which of the major ions (Na+, Ca2+, K+, Cl-, HCO3) regulate, and/or stimulate the various phases of acid secretion. The results of this study will allow us to develop a new model of acid secretion including newly defined transport proteins that were inaccessible before the development of our various techniques. These data will help us to design strategies of control for both hyper- and hypoacidity.

描述：（改编自研究者摘要）众所周知， 胃在消化食物中起着关键作用， 通过产生含有0.16N盐酸的溶液来破坏身体。 这种作用对生物体的正常生存至关重要。 的 H+离子穿过顶膜的传导运动起着关键作用 在酸性分泌中。 H+离子净流出与 K+离子的再循环使我们能够保持持续的酸通量， 在刺激胃酸分泌期间发生。 除了这一运动， 预计将观察到氯化物的平行流出，以帮助产生 腺腔中的酸。 酸的刺激损失发生在 H-K-ATP酶主动插入顶膜， 从细胞流出到腺腔。 细胞的变化 在非刺激状态下的腺体是完全未知的，由于 先前无法接近完整腺体的顶面。 关键 这项赠款的重点将是使用各种技术， 在我们的实验室开发的，以进入完整腺体的顶面 并检查酸分泌的生物物理学和调节 transcellularly，专注于从发展的变化， 非受刺激腺体到受刺激腺体。 我们将利用我们的发现， 解释什么变化是发展中国家的胃在这两个hyper-and 亚酸性状态，并检查哪些主要离子（Na+，Ca 2+，K+， Cl-、HCO 3）调节和/或刺激酸分泌的各个阶段。 这项研究的结果将使我们能够开发一种新的模型酸 分泌物，包括新定义的转运蛋白， 在我们的各种技术发展之前。 这些数据将帮助我们 设计控制胃酸过多和胃酸过少的策略。