POLYAMINES IN THE REGULATION OF GASTROINTESTINAL GROWTH

本提案的总体目标是研究和界定 多胺腐胺，亚精胺，精胺和尸胺 多胺腐胺、亚精胺、精胺和尸胺在 胃肠生长的调节。 肠道的生长 在体内和体外条件下进行了各种实验后， 诱导胃肠道生长的干预措施。 的作用 多胺的研究将在下列大纲下进行 具体目标：1. 研究和定义管腔内 用于原核和真核来源的多胺作为调节剂 粘膜生长 2. 研究胃肠电极化 上皮细胞和多胺在这些细胞中的矢量运动。 3. 研究各种生长因子的营养效应及其对生长的影响。 与胃肠道中多胺依赖性生长的关系。 理解这一过程的调节的重要性是 意识到许多胃肠道疾病 肠道实际上是粘膜生长障碍。 食管反流， 慢性胃炎，Zollinger-Ellison二氏粘膜过度增生。 的 聚胺是一组普遍分布的聚阳离子， 正常生长和分化所需;这项工作的目标是 阐明多胺在粘膜生长过程中的作用。 建议研究多胺的可用性， 无菌和无菌大鼠结肠微区系多胺代谢 设计了一些实验来研究腐胺的直接作用 刺激十二指肠隐窝细胞系（IEC-6）的DNA合成， 文化 IEC-6细胞系也将用于研究多胺 从该细胞的顶侧和基底侧摄取。 运动 多胺进入胃肠道上皮细胞将被证实在整个 动物 最后，建议将促生长效应与 各种营养因子调节多胺的能力 新陈代谢. 这些实验将用于确定是否 多胺在粘膜刺激过程中充当共同的介质， 增长，或者只是扮演一个放任的角色。

The overall objective of this proposal is to study and define the role of the polyamines putrescine, spermidine, spermine and cadaverine in the role of the polyamines putrescine, spermidine, spermine and cadaverine in the regulation of gastrointestinal growth. Growth of the gut will be studied under in vivo and in vitro conditions after various experimental interventions which induce gastrointestinal growth. The role of the polyamines will be studied under the outline provided by the following specific aims: 1. To study and define the role of intraluminal polyamines for prokaryotic and eukaryotic sources as regulators of mucosal growth. 2. To study the polarization of gastrointestinal epithelial cell and the vectorial movement of polyamines in these cells. 3. To study the trophic effects of various growth factors and their relationship to polyamine-dependent growth in the gastrointestinal tract. The importance of understanding the regulation of this process is underscored by the realization that many diseases of the gastrointestinal tract are, in fact, disorders of mucosal growth. Esophageal reflux, chronic gastritis, Zollinger-Ellison hyperproliferative mucosa. The polyamines are a group of ubiquitously distributed polycations which are required for normal growth and differentiation; the goal of this work is to elucidate the role of the polyamines during mucosal growth. It is proposed to study the availability of polyamines derived from colonic microfloral polyamine metabolism in gnotobiotic and axenic rats. Experiments have been designed to study the direct effects of putrescine to stimulate DNA synthesis in a duodenal crypt cell line (IEC-6) in culture. The IEC-6 cell line will also be used to study polyamine uptake from both apical and basolateral sides of this cell. The movement of polyamines into the GI epithelial cell will be confirmed in the whole animal. Finally, it is proposed to relate the growth promoting effects of various trophic factors to their ability to modulate polyamine metabolism. These experiments will be used to determine whether polyamines serve as a common mediator during stimulation of mucosal growth or if they serve only a permissive role.