MODULATION OF SALIVARY GLAND FUNCTION BY PROSTAGLANDINS

虽然唾液分泌主要由自主神经调节， 神经系统，有证据表明，其他因素可能会调节 唾液腺的分泌功能。 其中包括前列腺素， 其是普遍存在的生物活性脂肪酸衍生物， 影响多种组织和生理功能。 的 因此，该项目的总体长期目标是， PG作为唾液腺功能调节剂作用。 到 开始我们的这种调制的表征，我们提出的研究， 这一补助期旨在调查两个主要的影响， 前列腺素（PGE 1和PGF 2 α）及其相关物质 代谢（花生四烯酸，磷脂酶A2，磷脂酸） 唾液分泌机制的几个方面 和电解质。 以大鼠下颌下腺为模型系统， 我们建议首先描述各种剂量的 这些物质对胆碱能诱导的液体和电解质分泌的影响 和肾上腺素能药物。 影响 唾液体积、流速、电解质（Na、K、Cl、Ca）组成和 输出和分数导管重吸收和分泌将是 研究了 第二，根据目前对离子的了解， 唾液形成的机制，我们建议调查 PG和有关物质对分散体中离子运动的影响 通过腺体的酶消化分离的下颂腺泡。 我们 特别感兴趣的是那些离子运动， 导致唾液分泌的机制。 这些措施包括：a）释放和 K+的吸收; B）Cl的吸收和流出; c）Ca++的吸收和流出。 这些离子的同位素示踪剂将用于研究 测试物质的各种动力学参数，包括时间过程 相应的通量，同位素平衡的半衰期，初始 速率（即，速率常数）和最大通量（Jmax）。 相关性 这两种类型的实验结果之间应该提供更多的 关于PG调节主要方面的方式的详细信息 唾液腺分泌功能的一种，即分泌液体 和电解质（唾液的水溶性部分）。 这可以提供线索 关于这些物质在改变唾液腺功能中的作用， 病理条件（炎症，免疫反应），其中他们 组织水平受到疾病过程的干扰。

Although salivary secretions are primarily regulated by the autonomic nervous system, there is evidence that other factors may modulate the secretory functions of salivary glands. These include the prostaglandins, which are ubiquitous, biologically active fatty acid derivatives which affect a great variety of tissues and physiological functions. The overall, long-term objective of this project is, therefore, to characterize the role that PG play as modulators of salivary gland function. To initiate our characterization of this modulation, we propose studies for this grant period designed to investigate the effects of two major prostaglandins (PGE1 and PGF2alpha) and of substances involved in their metabolism (arachidonic acid, phospholipase A2, phosphatidic acid) on several aspects of the mechanism underlying the secretion of salivary fluid and electrolytes. Using the rat submandibular gland as the model system, we propose to first characterize the effects of a wide range of doses of these substances on fluid and electrolyte secretion induced by cholinergic and adrenergic agents in isolated, perfused gland preparations. Effects on saliva volumes, rates of flow, electrolyte (Na, K, C1, Ca) composition and outputs and fractional ductal reabsorption and secretion will be investigated. Second, based on what is currently known about the ionic mechanism underlying the formation of saliva, we propose to investigate the effects of the PG and related substances on ion movements in dispersed submandibular acini isolated by enzymatic digestion of the gland. We are particularly interested in those ion movements which are part of the mechanism leading to saliva secretion. These include: a) release and uptake of K+; b) uptake and efflux of Cl; c) uptake and efflux of Ca++. Isotopic tracers of these ions will be used to study the effects of the test substances on various kinetic parameters, including the time course of the respective flux, the half time for isotope equilibration, the initial rate (i.e., rate constants) and the maximum flux (Jmax). Correlations between the findings of both types of experiment should provide more detailed information about the manner in which PG modulate a major aspect of secretory function in salivary glands, namely, the secretion of fluid and electrolytes (the aqueous fraction of saliva). This can provide clues about the role of these substances in altering salivary gland function in pathological conditions (inflammation, immune reactions) in which their tissue levels are disturbed by the disease process.