权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

SECRETORY MECHANISMS IN THE SALIVARY GLANDS

唾液腺的分泌机制

基本信息

批准号：
2882709
负责人：
GUO HE ZHANG
金额：
$ 19.2万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-07-01 至 2001-02-28
项目状态：
已结题

项目摘要

The long-term objective of this project is to elucidate the mechanisms of water and electrolyte secretion in salivary acinar cells. This secretory response is associated with a signal transduction pathway that involves the turnover of membrane phosphoinositides, the mobilization of Ca2+ from intracellular and extracellular compartments and the activation by Ca2+ of monovalent ion fluxes (K, C1) that are critical for secretion. Our studies during the current grant period and those of others have demonstrated complex functional links in this pathway, some of which are only partially understood at present and may or may not operate with all stimuli that enhance salivary fluid and electrolyte secretion. Some elements of signal transduction may show, furthermore, unique features in salivary cells. Our general goal for the new grant period is, therefore, to explore in greater detail these functional associations in salivary cell signaling. Our specific aims are: 1) to investigate further the coupling between three types of receptors (cholinergic, alpha-adrenergic and substance P receptors and phosphoinositide turnover. This coupling occurs by GTP binding proteins in many cells but little information is available about G protein coupling in salivary cells. We will use immunoprecipitation, competitive radioligand binding and biochemical methods to identify the specific G proteins associated with each one of these receptors, 2) to characterize further the functional properties of Ca2+ storage sties and Ca2+ entry mechanisms and the manner in which they are affected by each type of stimulus. We will use spectrofluorimetric, imaging, isotopic and x-ray microprobe analysis techniques to evaluate changes in cell Ca2+ in the absence and presence of agonists and of substances that can modify the mobilization of internal or external Ca2+, 3) to explore further the functional link between K and C1 conductances and possible regulatory factors, including [Ca2+]i, G proteins, protein kinases and cADP ribose. We will use imaging, spectrofluorimetric, isotopic and x-ray diffraction techniques to measure changes in the content and transmembrane fluxes of K and C1 after exposure to the various agonists and of the substances listed above. We propose to compare these various parameters in control salivary acinar cells an in cells derived from rats treated chronically with drugs (reserpine, atropine) that modify receptor functions and, s shown in preliminary findings, downstream elements in the signaling pathway. These drug treatments cause reduced salivary secretion of fluid and are useful models for the study of salivary hypofunction and its possible relation to altered elements of the signaling pathway. A major cause of xerostomia in humans is the use of drugs acting as receptor antagonist and our studies would contribute to our understanding or normal salivary signaling and of how it may be affected by therapeutic agents.

该项目的长期目标是阐明唾液腺泡细胞分泌水和电解质。这个秘书反应与信号转导途径相关，该途径涉及膜磷酸肌醇的周转，Ca2+的动员细胞内和细胞外区室以及 Ca2+ 的激活对分泌至关重要的单价离子通量（K、C1）。我们的研究在当前的资助期内和其他人的资助期内已经证明该通路中的功能链接十分复杂，其中一些仅是部分的目前已了解，并且可能会也可能不会在所有刺激下起作用增强唾液和电解质的分泌。信号的一些要素此外，转导可能在唾液细胞中显示出独特的特征。我们的因此，新资助期的总体目标是探索更大范围的详细说明唾液细胞信号传导中的这些功能关联。我们的具体目标是：1）进一步研究三者之间的耦合受体类型（胆碱能、α-肾上腺素能和 P 物质受体和磷酸肌醇周转率。这种偶联是通过 GTP 结合发生的许多细胞中都有蛋白质，但有关 G 蛋白的信息很少唾液细胞中的耦合。我们将使用免疫沉淀、竞争性放射性配体结合和生化方法来鉴定特定的 G 与这些受体中的每一种相关的蛋白质，2) 来表征进一步研究 Ca2+ 储存区和 Ca2+ 进入的功能特性机制以及它们受每种类型影响的方式刺激。我们将使用荧光光谱、成像、同位素和 X 射线微探针分析技术评估细胞 Ca2+ 的变化激动剂和可以改变的物质的存在和不存在内部或外部 Ca2+ 的动员，3) 进一步探索 K 和 C1 电导之间的功能联系以及可能的监管因子，包括 [Ca2+]i、G 蛋白、蛋白激酶和 cADP 核糖。我们将使用成像、荧光分光光度法、同位素和 X 射线衍射测量 K 含量和跨膜通量变化的技术和 C1 暴露于各种激动剂和所列物质后多于。我们建议比较对照唾液中的这些不同参数长期接受药物治疗的大鼠体内的腺泡细胞（利血平、阿托品）可改变受体功能，并且，s 所示初步发现，信号通路中的下游元件。这些药物治疗会导致唾液分泌减少，并且是有用的研究唾液功能减退的模型及其可能的关系信号通路的元件发生改变。口干症的一个主要原因人类正在使用作为受体拮抗剂的药物，我们的研究将有助于我们理解正常的唾液信号传导以及它如何受到治疗药物的影响。