DEVELOPMENTAL ASPECTS OF UPPER GASTROINTESTINAL MOTILITY

上胃肠动力的发育方面

• 批准号: 3317859
• 负责人: A Craig HILLEMEIER
• 金额: $ 17.93万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3317859
• 关键词: acetylcholine; calcium flux; calmodulin; cats; cholecystokinin; growth /development; infant animal; intracellular transport; muscle contraction; muscle proteins; smooth muscle; stomach motility /pressure

Gastric motor dysfunction results in significant morbidity which is particularly striking during the newborn period. During growth and development the stomach is required to deal with changing dietary intake. The changes in dietary constituents during growth and development from predominantly liquid to mixed solid liquid meals places an increasing burden on the antrum which is required to triturate solids. The newborn antrum generates less force than adult antrum and our preliminary data indicate that newborn antral smooth muscle cells undergo biochemical changes that correlate with these changes in dietary intake. The specific aims of this proposal are to determine what developmental changes occur in the stomach, by examining specifically: 1) the source of calcium utilized for agonist induced contraction 2) the intracellular pathways which are followed during contraction 3) the contractile proteins responsible for generation of force. We will monitor changes in these parameters over the first 6 weeks of life in the kitten and compare them to the adult. We propose to study the maturation of the contractile response to cholinergic stimulation in the antrum which in the newborn is totally dependent on utilization of Ca from extracellular sources and proceeds via a calmodulin independent pathway to the adult antrum which is able to utilize Ca from both intracellular and extracellular sources and proceeds via a calmodulin dependent pathway. Concurrently we will study the quantitative and qualitative biochemical changes in the contractile proteins responsible for the generation of force. This developmental process is important for the transformation of the antrum into a region which is able to generate greater force and triturate solids. In summary we will focus on the hypothesis that during the growth process contractile agonists (acetylcholine and CCK-OP) may preferentially utilize different sources of Ca and activate different intracellular pathways. We can follow this maturational process during the period of infancy, at a time when the ability to handle changes in diet is crucial for optimal growth. We believe that this type of expertise and focus is critical to understanding the development of gastric motility during this transitional period. The studies outlined will shed new light on the maturation of the regulatory mechanisms responsible for gastric contraction.

胃运动功能障碍导致显著的发病率， 尤其是在新生儿时期。 在生长和 胃的发展需要处理不断变化的饮食 摄入 生长期日粮成分的变化， 由以流质为主发展为混合固体流质饮食场所 需要研磨的胃窦负担增加 固体 新生儿胃窦产生的力小于成人胃窦， 我们的初步数据表明，新生胃窦平滑肌细胞 经历与这些饮食变化相关的生化变化， 摄入 本提案的具体目的是确定 发育变化发生在胃，通过具体检查： 1)用于激动剂诱导的收缩的钙源2） 在收缩过程中遵循的细胞内途径3） 负责产生力的收缩蛋白质。 我们将 在出生后的前6周内监测这些参数的变化， 把小猫和成年猫做比较 我们建议研究 成熟的收缩反应胆碱能刺激在 新生儿的胃窦完全依赖于钙的利用 从细胞外来源，并通过钙调素独立 能够利用来自两种细胞的Ca的成人胃窦通路 细胞内和细胞外来源，并通过钙调蛋白 依赖路径 同时，我们将研究定量和 收缩蛋白质的生化变化 for the generation生成of force力. 这个发展过程很重要 为了将窦转变成能够 产生更大的力并研磨固体。 总之，我们将重点放在假设，在生长过程中， 过程收缩激动剂（乙酰胆碱和CCK-OP）可能 优先利用不同的钙源， 细胞内途径 我们可以跟踪这个成熟的过程， 婴儿时期，在这个时候，处理变化的能力， 饮食对最佳生长至关重要。 我们认为，这种类型的 专业知识和重点是至关重要的了解发展 在这个过渡期的胃动力。 研究概述 将为监管机制的成熟提供新的线索， 负责胃收缩。