P2 PURINOCEPTORS AND SALIVARY GLAND FUNCTION

描述(改编自申请人的摘要)：正常运作 保持唾液腺的健康对维持口腔健康是必不可少的。这份名单 与调节唾液腺有关的已确定的细胞外因子 分泌物继续增加。最近增加的包括细胞外 核苷酸，通过P2嘌呤受体起作用。而一个角色是 已知唾液腺中的配体门控离子通道P2受体 几年来，G蛋白偶联(GPC)P2的存在和活性 腺体中的受体不太容易被记录下来，尽管这些 受体存在于唾液来源的细胞系中。这些研究 在本申请中提出的是基于我们最近的克隆和表达 人P2嘌呤受体、GPC P2U亚型的第一个cDNAs 正常大鼠颌下腺P2受体活性的初步研究 (SMG)细胞。需要检验的假设是GPC P2嘌呤受体 P2U和P2Y亚型参与了唾液腺的调节 分泌，并且这些受体的表达和活性随着 腺体的发展和组织状况以及作为一种 暴露于激动剂的后果。还假设大鼠SMG 细胞表达容量敏感的氯离子通道，该通道参与 P2受体激动剂增强细胞调节性体积减少 唾液来源。具体目标是：1)评估与发展有关的 P2U和P2Y嘌呤受体的表达及其调节作用的变化 在大鼠唾液腺中，使用从不同动物中分离的腺细胞 AGEs；2)检查正常唾液腺破裂的影响 结构对P2U和P2Y受体的表达和活性的影响； 激动剂诱导的P2受体脱敏特性及评价 共同的磷酸化位点在脱敏中的作用 以及4)通过克隆和表达其cDNA来评价， 容量敏感性氯通道在HSG-PA唾液中的作用 细胞调节性体积减少(RVD)，这是一个由P2U强化的过程 受体激活。总而言之，这些研究将提供更全面的 P2受体在细胞周期调控中的作用 唾液分泌物以及参与表达的因素和 这些受体的活性。我们的最终目标是阐明 唾液P2受体在维持口腔健康中的作用。

DESCRIPTION (Adapted from the applicant's Abstract): The proper functioning of salivary glands is essential to the maintenance of oral health. The list of identified extracellular agents implicated in regulating salivary gland secretion continues to increase. Recent additions include extracellular nucleotides, working through P2 purinoceptors. While a role for ligand-gated ion channel P2 receptors in salivary glands has been known for several years, the presence and activity of G protein-coupled (GPC) P2 receptors in the glands has been less easily documented, although these receptors are present in cell lines of salivary origin. The studies proposed in this application are based on our recent cloning and expression of the first cDNA for a human P2 purinoceptor, the GPC P2U subtype and on initial studies of P2 receptor activity in normal rat submandibular gland (SMG) cells. The hypothesis to be tested is that the GPC P2 purinoceptor subtypes, P2U and P2Y, are involved in the regulation of salivary gland secretion and that the expression and activity of these receptors vary as a function of the state of development and organization of the glands and as a consequence of exposure to agonist. It is also hypothesized that rat SMG cells express volume-sensitive chloride channels that are involved in the regulatory volume decrease potentiated by P2 receptor agonists in cells of salivary origin. The specific aims are: 1) to assess development-related changes in the expression and regulatory role of P2U and P2Y purinoceptors in rat salivary glands, using gland cells isolated from animals of different ages; 2) to examine the effects of disruption of normal salivary gland structure on P2U and P2Y receptor expression and activity; 3) to characterize agonist-induced desensitization of P2 receptors and to evaluate the role in desensitization of consensus phosphorylation sites within these receptors; and 4) to evaluate, through cloning and expression of its cDNA, the contribution of volume-sensitive chloride channels in HSG-PA salivary cells to regulatory volume decrease (RVD), a process potentiated by P2U receptor activation. Together, these studies will provide a fuller appreciation of the role that P2 receptors play in the regulation of salivary secretion and of the factors involved in the expression and activity of these receptors. The ultimate goal is to elucidate the contributions salivary P2 receptors make to the maintenance of oral health.