DEVELOPMENTAL ASPECTS OF UPPER GASTROINTESTINAL MOTILITY

胃运动障碍会导致严重的发病率，这是 尤其是在新生儿时期。在成长过程中和 胃的发育需要应对饮食的变化 入口处。生长和发育过程中日粮成分的变化 从以液体为主向固液混合型餐饮场所发展 胃窦部的负担越来越重，需要进行反复的治疗 实体。新生儿的胃窦产生的力量比成人的胃窦小，而且 我们的初步数据显示，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 入口处。这项提案的具体目标是确定 发育变化发生在胃中，通过具体检查： 1)用于激动剂诱导收缩的钙的来源2) 收缩过程中遵循的细胞内通路3) 负责产生力量的收缩蛋白。我们会 监测这些参数在生命的前6周内的变化 并将小猫与成年猫进行比较。我们建议研究 大鼠对胆碱能刺激的收缩反应成熟 新生儿的胃窦完全依赖于钙的利用 来自细胞外来源，并通过不依赖钙调素的方式进行 通向成体胃窦的通路，该通路能够利用来自 通过钙调素的细胞内和细胞外来源和收益 依赖途径。同时，我们将研究定量和 与此相关的收缩蛋白的质化生化变化 用来产生力量。这一发展过程很重要。 将鼻腔转变为一个能够 产生更大的力，并形成固体。 总而言之，我们将重点关注这样一个假设，即在增长过程中 过程收缩激动剂(乙酰胆碱和CCK-OP)可能 优先利用不同来源的钙，激活不同的 细胞内通路。我们可以遵循这个成熟的过程 婴儿期，在这一时期，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 专业知识和重点对于理解 在这一过渡期内的胃运动。概述的研究 将为监管机制的成熟提供新的线索 负责胃部收缩。

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.