Regulation of Intestinal Na Absorption

肠道钠吸收的调节

• 批准号: 7460558
• 负责人: Uma Sundaram
• 金额: $ 25.78万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7460558
• 关键词: Affinity; Body Weight decreased; Cells; Characteristics; Chronic; Condition; Coupled; Data; Diarrhea; Electrolytes; Epithelial Cells; Gastrointestinal tract structure; Genetic Transcription; Glucose; Goals; Homeostasis; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Intestines; Laboratories; Link; Liquid substance; Malabsorption Syndromes; Malnutrition; Mediating; Mediator of activation protein; Membrane Protein Traffic; Membrane Transport Proteins; Modality; Modeling; Molecular; Morbidity - disease rate; Mucous Membrane; Na(+)-K(+)-Exchanging ATPase; Nitric Oxide; Numbers; Nutrient; Operative Surgical Procedures; Oryctolagus cuniculus; Pathway interactions; Patients; Phosphorylation; Physiological; Physiology; Production; Regulation; Research Personnel; Secondary to; Small Intestines; Staging; Transport Process; Villus; absorption; base; brush border membrane; glycosylation; insight; novel; programs; stem; symporter

DESCRIPTION (provided by applicant): The primary Na absorbing pathways in the mammalian small intestine are Na-glucose co-transport (SGLT-I) and coupled NaCI absorption. How constitutive nitric oxide (cNO), known to regulate many gastrointestinal tract functions, may regulate these important Na absorbing pathways in the normal mammalian small intestine is not well understood. Preliminary studies from our laboratory indicate that cNO uniquely regulates these two primary Na absorbing pathways in the small intestine in a complementary fashion to achieve cellular Na homeostasis. Our preliminary studies indicate that in physiological states cNO facilitates SGLT-1 by modulating its affinity for glucose whereas cNO represses NHE3 by modulating its transporter numbers. Given this background we hypothesize that cNO uniquely regulates primary Na absorbing pathways in the mammalian small intestine. Thus, the overall goal of this proposal is to determine the mechanism of regulation of Na absorption by nitric oxide in the normal mammalian small intestine. This study will shed novel insight into the active regulation of and decipher the mechanisms of modulation of essential Na absorbing transport processes by cNO in the normal intestine. It will also provide new insights into the cNO mediated intracellular regulation of these transport processes. Further, the results of these studies will set the stage to decipher the mechanism of regulation of these important Na absorptive pathways in inflammatory bowel disease (IBD). In IBD understanding the regulation of Na absorption is important since, it is known that morbidity of IBD stems from its effect on electrolytes, nutrients and fluid absorption; thus, patients with IBD sustain malabsorption and diarrhea with attendant malnutrition and weight loss. Better understanding of the mechanism of regulation of Na-absorbing transport processes by NO in the normal and chronically inflamed intestine will provide the basis for new and more efficacious treatment modalities for the malabsorption, diarrhea and malnutrition of IBD.

描述（由申请人提供）：哺乳动物小肠中的主要Na吸收途径是Na-葡萄糖共转移（SGLT-I）和偶联的NACI吸收。尚不清楚尚不清楚在正常哺乳动物小肠中调节这些重要的Na吸收途径的已知来调节许多胃肠道功能的构型一氧化氮（CNO）。我们实验室的初步研究表明，CNO以互补的方式独特地调节小肠中这两种主要的NA吸收途径，以实现细胞NA的稳态。我们的初步研究表明，在生理状态下，CNO通过调节其对葡萄糖的亲和力来促进SGLT-1，而CNO通过调节其转运蛋白数量来抑制NHE3。鉴于此背景，我们假设CNO独特地调节了哺乳动物小肠中的原发性NA吸收途径。因此，该提案的总体目标是确定正常哺乳动物小肠中一氧化氮对Na吸收的调节机制。 这项研究将使人们对正常肠中CNO的必需NA吸收运输过程的调节机制进行新的洞察力。它还将为CNO介导的这些运输过程的细胞内调节提供新的见解。此外，这些研究的结果将奠定阶段，以破译炎症性肠病（IBD）中这些重要NA吸收途径的调节机理。在IBD中，了解Na吸收的调节很重要，因为众所周知，IBD的发病率源于其对电解质，营养和液体吸收的影响。因此，IBD患者以伴随的营养不良和体重减轻而维持吸收不良和腹泻。在正常和长期发炎的肠道中，更好地理解了不吸收NA的运输过程的机制，这将为新的，更有效的治疗方式提供基础，以使IBD的不良吸收，腹泻和营养不良。