REGULATION OF NA, K/ATPASE BY SHORT CHAIN FATTY ACIDS

短链脂肪酸对 NA、K/ATP 酶的调节

• 批准号: 6078417
• 负责人: MARSHALL H MONTROSE
• 金额: $ 2.91万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6078417
• 关键词: animal tissue; basolateral membrane; enzyme activity; ion transport; laboratory rat; second messengers; short chain fatty acid; sodium ion; sodium potassium exchanging ATPase; tissue /cell culture

This grant seeks to determine the mechanism by which short-chain fatty acids (SCFAs) regulate Na efflux by the Na/K ATPase at the basolateral membrane of colonocytes. SCFAs are a major non-endocrine stimulator of transcellular Na absorption by the colon. There is evidence in the literature to suggest that increasing luminal SCFAs may be an effective combatant of diarrheal secretion and an effective therapy for inflammatory bowel disease. Work performed by the applicant (the subject of the current R01) demonstrated that stimulation of transcellular Na absorption by SCFAs involves activation of apical Na/H exchange. Transcellular Na transport requires a concomitant increase in Na efflux at the basolateral membrane presumably via a stimulation of the Na/K ATPase. The focus of this FIRCA grant is to confirm this putative increase in Na/K ATPase activity and to determine the mechanism by which its activity is increased by SCFAs. Preliminary data by the foreign PI indicates a persistent increase in Na/K ATPase activity following a 20 min exposure of cultured colonocytes (HT29-C1) cells to SCFAs. The foreign PI will further evaluate factors involved in this effect and determine if it results from a change in intracellular Na or pH (related to a stimulation of Na/H exchange) or from changes in the intracellular level second messengers such as cAMP or Ca2+. In addition, studies are proposed to evaluate possible interactions between regulation of Na/K ATPase by SCFAs and receptor antagonists of cAMP and calcium.

这项资助旨在确定短链脂肪 酸(SCFA)通过基底外侧Na/K ATPase调节Na外流 结肠细胞膜。单链脂肪酸是一种主要的非内分泌刺激因子。 结肠对钠的跨细胞吸收。有证据表明， 文献表明，增加腔内SCFA可能是一种有效的 止泻剂和治疗腹泻的有效方法 炎症性肠病。申请人所进行的工作( 当前R01的主题)显示了对 单链脂肪酸的跨细胞钠吸收涉及顶端Na/H的激活 交换。跨细胞的钠转运需要伴随的增加 在基底外侧膜上的NA外流可能是通过刺激 Na/K-ATPase。这笔FIRCA赠款的重点是确认这一点 Na/K-ATPase活性升高及其机制探讨 其活性可被单链脂肪酸提高。初步数据由政府统计处 外源性PI提示Na/K-ATPase活性持续升高 在培养的结肠细胞(HT29-C1)暴露20分钟后 SCFA。外国PI将进一步评估与此有关的因素 影响并确定它是否是由于细胞内Na或 PH(与Na/H交换的刺激有关)或 细胞内水平的第二信使，如cAMP或钙离子。此外, 建议进行研究，以评估可能的相互作用 单链脂肪酸及其受体拮抗剂对Na/K-ATPase的调节作用 钙。