GASTROINTESTINAL ENDOCRINOLOGY

胃肠内分泌学

• 批准号: 2693154
• 负责人: Courtney M Townsend
• 金额: $ 0.3万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-22 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2693154
• 关键词: GASTROINTESTINAL; ENDOCRINOLOGY

The long-term goal of this program is to provide useful new information on the mechanisms by which gastrointestinal hormones (GIH) and calcium- regulatory peptides influence body function. We will study gene expression, synthesis, storage, release, transport and mechanisms of action on target cells, hormone-hormone interrelationships, the target cell responses, and gene expression as regulated by these agents. The project by Dr. Thompson will study the role (both cause and effect) that GIH play in the aging of the gut. We plan to define some of the mechanisms involved in age-related changes in growth, secretion and gene expression of the GI tract. We will examine the role of GI hormones in regulating apoptosis in gut mucosa. We plan to study the effects of chronic caloric restriction as an anti-aging strategy. The project by Dr. Greeley will examine the role of chromogranin A (CGA) and the mechanisms by which CGA is processed to pancreastatin in enteroendocrine cells. We will study the regulation of CGA homeostasis and co-resident peptides. We will examine the role of prohormone convertases, and determine whether CGA co-resides with gastrin peptides and parathyroid hormone-related peptide (PTHrP) in pancreatic, colon, ovarian and liver cancer cells and whether CGA and co-resident peptides exhibit properties of regulated secretion. The project by Dr. Townsend will examine the effects of bombesin (BBS) on gene expression and release of the peptide, neurotensin. We will examine specific receptor and signal transduction pathways by which BBS affects peptide gene expression, peptide release and growth release and growth of GI cells. We will determine whether specific receptors and receptor-linked signal transduction pathways are different for each of these functions. We will examine both cells that express BBS receptors as well as human cells transfected with GRP or neuromedin B receptors and receptor mutants to dissect these pathways. We have found that the same GIH may either stimulate or inhibit growth of cancer cells. These studies will allow us to determine precisely the cell-specific mechanisms by which GIH affect growth of human cancer cells. The project by Dr. Cooper will examine the hypothesis that calcium-regulatory peptides, specifically PTHrP, play important regulatory roles in the gut. We will identify the mechanisms by which PTHrP regulates growth and differentiation of epithelial cells. We will determine whether PTHrP is an autocrine/paracrine regulatory agent and examine the effects of PTHrP on apoptosis in gut cells, and the role of PTHrP in regenerating liver. We will examine intracellular mechanisms by which vasoactive intestinal peptide (VIP) and PTHrP both stimulate cyclic AMP and ornithine decarboxylase mRNA activity and yet have opposite effects on growth of human colon cancer cells. Since the last competitive review we have demonstrated the productivity of our collaborating efforts by our publications: many publications relate to more than one project. With the support of this grant, our studies have evolved from whole animals to cellular, subcellular and molecular mechanisms of actions of GI hormones in order to meet the long-term objectives of our program.

该计划的长期目标是提供有用的新信息 关于胃肠激素（GIH）和钙的机制 调节肽会影响人体功能。 我们将研究基因 表达，综合，存储，释放，运输和机制 对靶细胞，激素激素相互关系的作用，目标 细胞反应和基因表达受这些药物调节。 这 汤普森博士的项目将研究该角色（因果关系） GIH在肠道衰老中发挥作用。 我们计划定义一些 与年龄相关的生长，分泌和基因变化涉及的机制 胃肠道的表达。 我们将研究GI激素在 调节肠粘膜凋亡。 我们计划研究 慢性热量限制是一种抗衰老策略。 项目是 Greeley博士将研究铬烷蛋白A（CGA）和 CGA在肠内分泌中加工到胰腺蛋白的机制 细胞。 我们将研究CGA稳态和共同居民的调节 肽。 我们将研究激素转化酶的作用，以及 确定CGA是否与胃肽和甲状旁腺共渗透 胰腺，结肠，卵巢和肝脏中与激素相关的肽（PTHRP） 癌细胞以及CGA和共同居民是否具有特性 受监管的分泌物。 汤森博士的项目将检查 孟买（BBS）对肽的基因表达和释放的影响， 神经素。 我们将检查特定的受体和信号转导 BBS影响肽基因表达，肽释放的途径 胃肠道细胞的生长释放和生长。 我们将确定是否 特定的受体和受体连接的信号转导途径是 这些功能中的每一个都不同。 我们将检查两个细胞 表达BBS受体以及用GRP转染的人类细胞或 神经蛋白B受体和受体突变体剖析这些途径。 我们发现相同的GIH可能会刺激或抑制生长 癌细胞。这些研究将使我们能够准确确定 GIH影响人类癌症生长的细胞特异性机制 细胞。 库珀博士的项目将探讨以下假设 钙调节肽，特别是PTHRP，发挥重要作用 肠道中的调节作用。 我们将确定该机制 PTHRP调节上皮细胞的生长和分化。 我们将 确定PTHRP是否是自分泌/旁分泌调节剂，并且 检查PTHRP对肠道细胞凋亡的影响，以及 PTHRP在再生肝脏中。 我们将检查细胞内机制 血管活性肠肽（VIP）和PTHRP都刺激 环状AMP和鸟氨酸脱羧酶mRNA活性，但已有 对人结肠癌细胞生长的影响相反。 自上次 竞争评论我们已经证明了我们的生产力 我们出版物的合作努力：许多出版物都与 一个以上的项目。 在这笔赠款的支持下，我们的研究有 从全动物演变为细胞，亚细胞和分子 GI激素的作用机制，以满足长期 我们计划的目标。