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调节 唾液腺的分泌功能。其中包括前列腺素， 它们是普遍存在的具有生物活性的脂肪酸衍生物 影响多种组织和生理功能。这个 因此，总体来说，该项目的长期目标是 PG作为唾液腺功能调节剂的作用。至 开始我们对这种调制的表征，我们建议研究 这一赠款期间旨在调查两个主要因素的影响 前列腺素(前列腺素E_1和前列腺素F_2α)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 还有电解液。以大鼠颌下腺为模型系统， 我们建议首先描述大范围剂量的 这些物质对胆碱能引起的液体和电解质分泌的影响 以及离体腺制剂中的肾上腺素能药物。对……的影响 唾液量、流率、电解质(钠、钾、氯、钙)组成和 输出量和部分导管重吸收和分泌 调查过了。第二，基于目前所知的离子 唾液形成的潜在机制，我们建议研究 PG及相关物质对分散体中离子运动的影响 颌下腺的腺体通过酶消化分离出来。我们是 对那些离子运动特别感兴趣，这些离子运动是 导致唾液分泌的机制。这些措施包括：a)释放和 K+的吸收；b)氯的吸收和流出；c)Ca++的吸收和流出。 这些离子的同位素示踪将被用来研究 测试物质的各种动力学参数，包括时间进程 各自的通量，同位素平衡的一半时间，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 关于PG调制主要方面的方式的详细信息 唾液腺的分泌功能，即分泌液体 和电解质(唾液的含水部分)。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 病理状态(炎症、免疫反应) 组织水平会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.