WATER AND ELECTROLYTE TRANSPORT BY THE INTESTINE

肠道的水和电解质运输

• 批准号: 3226133
• 负责人: KENNETH A. HUBEL
• 金额: $ 11.67万
• 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 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3226133
• 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.

第一部分建议进行研究，以确定 肠神经系统对电解质和水的转运 家兔的小肠和大肠。 先前的研究 显示刺激肠神经（可能是粘膜下 神经元）减少人回肠和乙状结肠中的氯化物吸收 结肠，并导致空肠和盲肠分泌氯化物。 将继续对3个假设进行检验：1）刺激（化学或 机械的）引起运输的变化，部分地， 通过肠神经反射; 2）通过这种反射， 某些粘膜刺激物可改变某些部位的离子和液体转运 远离刺激部位; 3）离子反应 运输将有所不同，这取决于所研究的部分是否 是从刺激的节段向外或向外。 这些刺激因素 所研究的是机械的（扩张）和化学的（胆汁盐， 血清素、E. coli ST毒素和茶碱）。 运输将 通过标准方法在麻醉家兔中进行研究， 测量离子通量和电指数在一个专门设计的 通量室 在第二部分中，我们将确定肽对 通过人小肠和大肠的粘膜转运 由肠上皮细胞上的受体直接介导，或间接介导 通过释放二级神经递质 的肽 存在于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 在手术获得的组织中， 并安装在标准通量室中，我们 将评估神经调解，通过确定是否 降低了肽引起的短路电流变化 神经毒素河豚毒素 如果是的话，我们将尝试识别 该传递剂与特异性拮抗剂，例如，假定阿托品 VIP拮抗剂，或通过脱敏。 这种研究 监测递质释放的补充研究 免疫化学（其他人）通过证明生物学 这种释放的效果。 需要对人体组织进行研究，因为 物种的多样性。