REGULATION OF UROGUANYLIN BY DIETARY ZINC STATUS

这一修订后的申请建议扩大观察这些 研究人员发现， 会因缺锌而上调 Uroguanylin是一种肠道 一种激素，其受体鸟苷酸环化酶-C起重要作用 调节肠道液体平衡。的文献报告 补充锌可以纠正分泌性腹泻， 尿鸟苷素与锌缺乏。 该项目的目标是 描述锌治疗期间尿鸟苷素诱导的真正原因 缺乏大鼠，并确定这是否可以提供 锌补充剂逆转临床方面的机制 分泌性腹泻 修订建议的六个具体目标是 上市1)锌对尿鸟苷素mRNA表达调控的时程 不足之处将予以确定。 2)锌对尿鸟苷素mRNA的调控 将表征充满。 3)将使用原位杂交技术 以确定哪些细胞类型表达尿鸟苷素前体。 4)使用 最近制备的抗体，尿鸟苷素前体的水平将是 与尿鸟苷素mRNA水平相关。 5)使用原位连接的环， 饮食不足对肠液分泌的影响将是 评估。 6)研究人员建议开始用T-84细胞进行研究 或Caco-2细胞，以测试培养基锌浓度对 尿鸟苷素前体mRNA和/或肽水平。

This revised application proposes to extend the observation of these researchers that the precursor mRNA for the peptide hormone uroguanylin is up-regulated by zinc deficiency. Uroguanylin is an intestinal hormone whose receptor, guanylate cyclase-C, plays a significant role in regulating intestinal fluid balance. Literature reports that supplemental zinc can correct secretory diarrhea and thus links uroguanylin with zinc deficiency. The objective of this project is to characterize the true causes of uroguanylin induction during zinc deficiency in rats, and to determine whether this could provide the mechanism by which Zn supplementation reverses the clinical sides of secretory diarrhea. Six specific aims in the revised proposal are listed. 1) The time course of uroguanylin mRNA regulation by zinc during deficiency will be determined. 2) Uroguanylin mRNA regulation by zinc repletion will be characterized. 3) In situ hybridization will be used to determine which cell types express uroguanylin precursor. 4) Using recently prepared antibodies, levels of uroguanylin precursor will be related to levels of uroguanylin mRNA. 5) Using in situ ligated loops, the effect of dietary deficiency on intestinal fluid secretion will be evaluated. 6) The researchers proposed to begin studies with T-84 cells or Caco-2 cells to test the impact of media zinc concentration on uroguanylin precursor mRNA and/or peptide levels.