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: 6188539
• 负责人: MARSHALL H MONTROSE
• 金额: $ 2.7万
• 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/6188539
• 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.

该赠款旨在确定短链脂肪的机制 酸 (SCFA) 通过基底外侧的 Na/K ATP 酶调节 Na 流出 结肠细胞膜。 SCFA 是一种主要的非内分泌刺激剂 结肠对钠的跨细胞吸收。有证据在 文献表明增加管腔 SCFA 可能是一种有效的方法 腹泻分泌物的对抗剂和有效的治疗方法 炎症性肠病。 申请人所做的工作（ 当前 R01 的主题）证明了刺激 SCFA 的跨细胞 Na 吸收涉及顶端 Na/H 的激活 交换。跨细胞 Na 转运需要同时增加 Na 可能通过刺激基底外侧膜流出 Na/K ATP 酶。 FIRCA 赠款的重点是确认这一点 Na/K ATP酶活性的推定增加并确定其机制 SCFA 会增加其活性。初步数据由 外源 PI 表明 Na/K ATP 酶活性持续增加 将培养的结肠细胞 (HT29-C1) 暴露于 20 分钟后 SCFA。 国外PI将进一步评估此事涉及的因素 效应并确定其是否是由细胞内Na或的变化引起的 pH（与 Na/H 交换的刺激有关）或来自 细胞内水平的第二信使，例如 cAMP 或 Ca2+。此外， 建议进行研究以评估之间可能的相互作用 SCFA 和 cAMP 受体拮抗剂对 Na/K ATP 酶的调节 钙。