BIOPHYSICAL PRINCIPLES OF PERISTALTIC PHENOMENA

胃肠道括约肌保持关闭，维持持续的 压力，并放松以允许推注通过。 我们会研究 负责维护压力屏障及其 在放松的过程中。 1)由食管下括约肌和内括约肌产生的张力 肛门括约肌是肌源性的，因为它不被神经阻滞剂消除 河豚毒素 负责维持这一持续的机制 紧张性收缩尚未阐明。 我们将研究 钙在阶段性食管收缩和维持低 食管括约肌紧张 我们将检验相位 食管的收缩完全依赖于细胞外钙， 而食管下括约肌的紧张性取决于细胞内钙。 这一假说可能与理解损伤机制有关 在急性实验性食管反复酸灌注中产生 食管炎 我们还将测试其与慢性实验性 食管炎 2)舒张是由非肾上腺素能非胆碱能抑制性 神经元，但神经递质的确切性质尚不清楚。 我们将 研究某些神经肽在神经源性松弛中的作用。 我们和 其他研究表明，VIP可能参与神经源性舒张， 食管下括约肌 最近，我们发现VIP可能是 负责放松肛门内括约肌。 其他肽 VIP家族（PHI，GRF）和一种新肽（NPY）将被测试， 评估作为神经性放松参与者的可能作用， 在蠕动扫描之前的下行抑制中。 我们将 探索这些肽产生抑制的机制， 肠平滑肌 在某些组织中，VIP和PHI激活腺苷酸 环化酶与组织中cAMP含量增加有关，但与VIP 而LES松弛过程中的cAMP尚未建立。 此外，委员会认为， 最近的证据表明，环GMP在平滑肌中的可能作用 放松. 我们建议研究cAMP和cGMP在LES中的作用 以及它们与这些神经肽的关系。

Gastrointestinal sphincters remain closed, maintaining a sustained pressure, and relax to allow the passage of a bolus. We will examine the mechanisms responsible for maintenance of the pressure barrier and its abolition during relaxation. 1) The tonus generated by the lower esophageal sphincter and the internal anal sphincter is myogenic as it is not abolished by the neural blocker tetrodotoxin. The mechanisms responsible for maintenance of this sustained tonic contraction have not been clarified. We will examine the role of calcium in phasic esophageal contraction and in maintenance of lower esophageal sphincter tonus. We will test the hypothesis that phasic contraction in the esophagus depends entirely on extracellular calcium, while lower esophageal sphincter tonus depends on intracellular calcium. This hypothesis may be relevant to understanding the mechanism of injury produced by repeated acid perfusion of the esophagus in acute experimental esophagitis. We will also test its relevance to chronic experimental esophagitis. 2) Relaxation is mediated by non-adrenergic non-cholinergic inhibitory neurons but the exact nature of the neurotransmitter is not known. We will examine the role of some neuropeptides in neurogenic relaxation. We and others have shown that VIP may be involved in neurogenic relaxation of the lower esophageal sphincter. Recently, we have shown that VIP may be responsible for relaxation of the internal anal sphincter. Other peptides of the VIP family (PHI, GRF) and a new peptide (NPY) will be tested to assess a possible role as participants in neurogenic relaxation as well as in the descending inhibition that preceeds peristaltic sweep. We will explore the mechanism by which these peptides produce inhibition of intestinal smooth muscle. In some tissues VIP and PHI activate adenylate cyclase and increase tissue content of cAMP, but a relationship between VIP and cAMP during LES relaxation has not been established. Furthermore, recent evidence suggests a possible role of cyclic GMP in smooth muscle relaxation. We propose to examine the role of cAMP and cGMP in LES relaxation and their relationships to these neuropeptides.