BIOPHYSICAL PRINCIPLES OF PERISTALTIC PHENOMENA

食道返流是一种常见的疾病，影响儿童和儿童中的一种。 十个成年人，如果不治疗可能会导致慢性食管炎， 吸入性肺炎、食道狭窄和Barretts食道 癌前状态。虽然食管炎是一种多因素疾病 这可能取决于不适当的放松，食道的速度 清除、粘膜阻力等因素，损害下 食道括约肌(LES)压力是患者的常见症状。 抱怨慢性胃灼热。 在肌条和单细胞中获得的初步数据表明 A)括约肌压力，主要是肌源性的，由 环状肌层的自发收缩是由 细胞内钙离子的持续释放，而食道 收缩依赖于细胞外钙离子通过电压内流。 依赖的钙离子通道，b)机制的损伤 细胞内钙离子的储存或释放可能是导致 诱导实验性食管炎后观察到LES张力丧失。 我们现在建议定义食道的致病机制 正常食道和LES中LES张力的收缩和维持， 并在一个实验模型中确定它们是如何受到影响的 食管炎。 A)在正常的LES和食道中，我们将检查 钙离子的释放和内流，肌醇磷脂的循环，以及 一些可能的钙调素和蛋白激酶C拮抗剂对血管紧张素转换酶的影响 LES静息状态及对食道和LES收缩反应的影响 激动剂。这些数据将阐明钙离子和肌醇的作用 磷酸盐在维持正常LES和食道功能中的作用 为定义食管炎发生的变化提供基础。 B)我们将确定LES静息音调和食道及LES 对激动剂的收缩反应受诱导 猫实验性食管炎。我们会确认在食管炎中 细胞内钙离子储存和释放的机制 是受影响的，但那些调节细胞外钙离子内流的人不受影响， 我们将研究肌醇磷脂循环的变化， 它们被认为是导致细胞内钙离子释放的原因 商店。这些数据将定义钙处理机制的变化， 在与食管炎相关的肌醇磷脂循环中， 将阐明LES和食道功能的关系以及 酸引起的损害，并可能为其预防提供理论依据。

Esophageal reflux is a common condition that affects children and one in ten adults, and if untreated may result in chronic esophagitis, aspiration pneumonia, esophageal strictures, and Barretts esophagus, a premalignant condition. Although esophagitis is a multifactorial disease that may depend on inappropriate relaxation, speed of esophageal clearance, mucosal resistance and other factors, impairment of Lower Esophageal Sphincter (LES) pressure is a common finding in patients complaining of chronic heartburn. Preliminary data obtained in muscle strips and in single cells suggest that a) sphincter pressure, which is primarily myogenic and maintained by spontaneous contraction of the circular muscle layer, is mediated by continuous release of Ca++ from intracellular stores whereas esophageal contraction depends on influx of extracellular Ca++ through voltage- dependent Ca++ channels, b) damage to the mechanisms responsible for either storage or release of intracellular Ca++ may be the cause of the loss of LES tone observed after induction of experimental esophagitis. We now propose to define the mechanisms responsible for esophageal contraction and maintenance of LES tone in the normal esophagus and LES, and determine how they are affected in a model of experimental esophagitis. a) In the normal LES and esophagus we will examine the time course of Ca++ release and influx, the cycling of inositol phospholipids, and the effect of some putative calmodulin and protein kinase C antagonists on LES resting tone and on esophageal and LES contraction in response to agonists. These data will clarify the role of Ca++ and inositol phosphates in maintenance of normal LES and esophageal function, and provide the groundwork to define changes occurring with esophagitis. b) We will determine how LES resting tone and esophageal and LES contraction in response to agonists are affected by induction of experimental esophagitis in the cat. We will confirm that in esophagitis the mechanisms responsible for storage and release of intracellular Ca++ are affected, but those regulating influx of extracellular Ca++ are not, and we will investigate changes in the cycling of inositol phospholipids, which are thought to be responsible for release of intracellular Ca++ stores. These data will define changes in calcium handling mechanisms, and in cycling of inositol phospholipids associated with esophagitis, will clarify the relationship between LES and esophageal function and acid induced damage, and may provide a rationale for its prevention.