WATER AND ELECTROLYTE TRANSPORT BY THE INTESTINE

肠道的水和电解质运输

• 批准号: 3226131
• 负责人: KENNETH A. HUBEL
• 金额: $ 11.24万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3226131
• 关键词: autonomic nervous system; bacterial toxins; biological fluid transport; electrolytes; gastrointestinal absorption /transport; gastrointestinal toxin absorption; intestinal mucosa; intestines; ion transport; laboratory rabbit; neurons; neurotransmitters; secretion; serotonin; theophylline

Studies are proposed in Part I to determine the influence of the enteric nervous system on the transport of electrolytes and water by the small and large intestine of rabbit. Previous studies have shown that stimulation of the enteric nerves (probably submucous neurons) reduces chloride absorption in human ileum and sigmoid colon, and causes secretion of chloride in jejunum and cecum. Tests of 3 hypotheses will be continued: 1) Stimuli (chemical or mechanical) that evoke changes in transport do so, in part, through enteric neural reflexes; 2) By means of such reflexes, some mucosal stimuli can alter ion and fluid transport at sites remote from the site of stimulation; and 3) A response in ion transport will differ depending upon whether the segment studied is orad or aborad from the stimulated segment. The stimuli to be studied are mechanical (distension) and chemical (bile salts, serotonin, E. coli ST toxin and theophylline). Transport will be studied by standard methods in anesthetized rabbits and by measuring ion fluxes and electrical indices in a specially-designed flux chamber. In part II, we will determine whether the effects of peptides on transport by the mucosa of the human small and large intestine are mediated directly by receptors on enterocytes, or indirectly by release of secondary neurotransmitters. Peptides that are present in varicosities or nerve endings arising from fibers of the myenteric plexus will be studied because of their probable physiological relevance. In tissues obtained at surgery, stripped of muscularis propria and mounted in a standard flux chamber, we will asssess the neural mediation by determining whether the short-circuit current change induced by the peptide is reduced with the neurotoxin, tetrodotoxin. If it is, we will try to identify the transmitter with specific antagonists, e.g., atropine, putative VIP antagonists, or by desensitization. Such studies should complement studies of transmitter release monitored immunochemically (by others) by demonstrating a biological effect of such release. Study of human tissues is required because of species variability.

第一部分提出了研究以确定 肠神经系统对电解质和水的运输 由兔子的小肠和大肠组成。 之前的研究有 研究表明，刺激肠神经（可能是粘膜下神经） 神经元）减少人类回肠和乙状结肠的氯吸收 结肠，并导致空肠和盲肠分泌氯化物。 将继续测试 3 个假设：1）刺激（化学或 机械）引起交通变化，部分原因是， 通过肠神经反射； 2）通过这样的反射， 一些粘膜刺激可以改变部位的离子和液体运输 远离刺激部位； 3) 离子响应 交通将根据所研究的部分而有所不同 是在受刺激的段之外或之外。 所要的刺激 研究的是机械（扩张）和化学（胆汁盐， 血清素、大肠杆菌 ST 毒素和茶碱）。 交通将 通过标准方法在麻醉兔子中进行研究 在专门设计的仪器中测量离子通量和电指数 通量室。 在第二部分中，我们将确定肽是否对 通过人体小肠和大肠粘膜运输 由肠细胞上的受体直接介导，或间接介导 通过释放次级神经递质。 肽是 存在于静脉纤维引起的静脉曲张或神经末梢 将研究肌间神经丛，因为它们可能 生理相关性。 在手术中获得的组织中，剥离 固有肌层并安装在标准通量室中，我们 将通过确定是否 肽引起的短路电流变化减少 与神经毒素，河豚毒素。 如果是，我们将尝试识别 具有特定拮抗剂的递质，例如阿托品，推定 VIP拮抗剂，或通过脱敏。 此类研究应该 监测递质释放的补充研究 免疫化学（由其他人）通过证明生物 这种释放的效果。 需要对人体组织进行研究，因为 物种变异性。