POLYAMINES IN THE REGULATION OF GASTROINTESTINAL GROWTH

多胺调节胃肠生长

• 批准号: 3447277
• 负责人: EDWARD R SEIDEL
• 金额: $ 3.81万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1987-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447277
• 关键词: Zollinger Ellison syndrome; autonomic nervous system; cell growth regulation; enteric bacteria; fatty acids; gastritis; gastrointestinal epithelium; gastrointestinal hormones; gastrointestinal neoplasms; gastrointestinal system; growth /development; hormone regulation /control mechanism; intestinal mucosa; pernicious anemia; polyamines; postnatal growth disorder

The presence of food in the gut produces both direct and indirect effects on the growth of the gastrointestinal mucosa. Becasue ingestion of foodstuffs leads to increased desquamation of the epithelium and changes in luminal or local nutrition, direct effects on growth are produced when food moves through the gut after a meal. Indirect effects of a meal include release of GI hormones, increased secretions and increased activity of the autonomic nervous system. There may be a common mechanism which mediates both types of stimulation. The polyamines are a group of ubiquitously distributed polycations which are required for normal cell growth and proliferation. Preliminary studies have shown that they are involved in the regulation of mucosal growth. These data demonstrate that 1) there is a proximal to distal gut gradient of polyamine metabolism, 2) the aliphatic amine, ethylamine, has direct trophic effects in the gut, 3) the trophic response to intestinal obstruction has, as a required event, the induction of polyamine metabolism. These observation may explain 1) the proximal to distal gut gradient of villus height and crypt depth, 2) the role of amines, both aliphatic and polyamines, as regulators of GI mucosal growth, 3) the mechanism whereby the hormones of the gut exert their trophic in GI tissues, and 4) the as yet unexplained adaptive response of the gut to intestinal surgery. It is proposed to study and define the role of amines as regulators of mucosal growth. Initial experiments are designed to localize the areas of the gut in which amine metabolism is important to growth. It will also be necessary to study amine metabolism in the bacteria of the intestinal microflora as amines secreted from these cells may have direct effects on mucosal growth. It will be determined whether the hormones of the GI tract induce polyamine metabolism and whether this step is required for expression of their trophic effects. Finally, the role of amines as mediators of the adaptive response to intestinal surgery will be defined in various animal models of postsurgical hyperplasia and hypertrophy. The importance of a thorough understanding of GI growth is underscored by the realization that many diseases of the bowel, e.g., Zollinger-Ellison syndrome, chronic gastritis, pernicious anemia and the growth of cancers of the alimentary canal, are accompanied by disorders of gastrointestinal growth.

食物在肠道中的存在会产生直接和间接的影响 对胃肠粘膜生长的影响。因为摄入了 食物会导致上皮细胞脱屑增加，并导致 腔内或局部营养，对生长产生直接影响的食物 在用餐后通过肠道。一顿饭的间接影响包括 胃肠激素的释放，分泌物的增加和细胞活性的增强 植物性神经系统。可能有一种共同的机制来调解 两种类型的刺激。多胺是一类普遍存在的 分布的聚阳离子是正常细胞生长所必需的 扩散。初步研究表明，它们参与了 对粘膜生长的调节。这些数据表明，1)存在 多胺代谢的近端至远端肠道梯度，2)脂肪族 胺，乙胺，对肠道有直接的营养作用，3)营养 对肠梗阻的反应，作为一个必要的事件，诱导 多胺新陈代谢。这些观察可以解释1)近端 远端肠道倾斜度对绒毛高度和隐窝深度的影响 脂肪胺和多胺，作为胃肠道粘膜生长的调节剂， 3)肠道激素在胃肠道发挥营养作用的机制 组织，以及4)肠道对 肠道手术。建议研究和定义胺的作用。 作为粘膜生长的调节剂。最初的实验旨在 确定肠道中胺代谢重要的区域 成长。还有必要研究人体内的胺代谢。 肠道微生物区系中的细菌，作为从这些细胞分泌的胺 可能对粘膜生长有直接影响。将确定是否 胃肠道的荷尔蒙诱导多胺代谢，以及这是否 它们的营养效应的表达需要步骤。最后， 胺在肠道手术适应性反应中的中介作用 将在各种术后增生性疾病的动物模型中定义 肥大。彻底了解GI增长的重要性在于 强调的是认识到许多肠道疾病，例如， Zollinger-Ellison综合征、慢性胃炎、恶性贫血和 消化道癌的生长，伴随着 胃肠道生长。