Regulation of Intestinal Na Absorption

描述（由申请人提供）：哺乳动物小肠中的主要钠吸收途径是Na-glucose co-transport （SGLT-I）和偶联的NaCI吸收。一氧化氮（cNO）是如何调节正常哺乳动物小肠中这些重要的钠吸收途径的，目前尚不清楚。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钠吸收途径，以实现细胞钠稳态。我们的初步研究表明，在生理状态下，cNO通过调节SGLT-1对葡萄糖的亲和力来促进SGLT-1，而cNO通过调节其转运体数量来抑制NHE3。基于这一背景，我们假设cNO独特地调节哺乳动物小肠的主要钠吸收途径。因此，本研究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。

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.