BIOPHYSICAL PRINCIPLES OF PERISTALTIC PHENOMENA

食管反流是一种常见的条件，影响儿童和一个在 十个成年人，如果不治疗可能导致慢性食管炎， 吸入性肺炎、食管狭窄和巴雷特食管， 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，食管的速度 清除率、粘膜抵抗力等因素，降低 食管括约肌（LES）压力是患者的常见发现 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，其主要是肌源性的，并由 环形肌肉层的自发收缩，由 Ca++从细胞内储存持续释放，而食管 收缩依赖于细胞外Ca++通过电压的流入， 依赖性Ca++通道，B）对负责 细胞内Ca ~（++）的储存或释放可能是导致细胞内Ca ~（++）浓度升高的原因。 诱导实验性食管炎后观察到LES张力的丧失。 我们现在建议确定食管癌的机制， 正常食管和LES中LES张力的收缩和维持， 并确定它们是如何在实验模型中受到影响的。 食管炎 a）在正常LES和食管中，我们将检查 Ca++的释放和内流，肌醇磷脂的循环， 一些推定钙调蛋白和蛋白激酶C拮抗剂对 LES静息张力和对食管和LES收缩的响应 激动剂 这些数据将阐明Ca++和肌醇的作用 磷酸盐维持正常LES和食管功能，以及 为定义食管炎发生的变化提供基础。 B）我们将确定LES静息张力和食管和LES 对激动剂的反应性收缩受到诱导的影响， 实验性食管炎的猫。我们将证实，在食管炎 负责细胞内Ca++储存和释放的机制 受到影响，但那些调节细胞外Ca++内流的细胞不受影响， 我们将研究肌醇磷脂循环的变化， 它们被认为负责细胞内Ca++的释放 店 这些数据将定义钙处理机制的变化， 以及在与食管炎相关的肌醇磷脂循环中， 将阐明LES与食管功能之间的关系， 酸引起的损害，并可能提供一个合理的预防。

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.