P2 PURINOCEPTORS AND SALIVARY GLAND FUNCTION

描述（改编自申请人的摘要）：适当的功能 唾液腺的分泌对维持口腔健康至关重要。 名单 已鉴定的参与调节唾液腺的细胞外因子 分泌物继续增加。 最近增加的内容包括细胞外 核苷酸，通过P2嘌呤受体起作用。 虽然角色为 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记录，尽管这些 受体存在于唾液来源的细胞系中。 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嘌呤受体的第一个cDNA，GPC P2 U亚型， 正常大鼠下颌下腺P_2受体活性初步研究 (SMG)细胞 待检验的假设是GPC P2嘌呤受体 亚型P2 U和P2 Y参与唾液腺的调节 这些受体的表达和活性随时间而变化。 腺体的发育和组织状态的功能， 暴露于激动剂的后果。 还假设大鼠SMG 细胞表达体积敏感性氯离子通道， P2受体激动剂增强的调节体积减少 唾液来源。 具体目标是：（1）评估与发展有关的 P2 U和P2 Y嘌呤受体表达和调节作用的变化 在大鼠唾液腺中，使用从不同动物中分离的腺细胞， 年龄; 2）检查正常唾液腺破坏的影响 结构对P2 U和P2 Y受体表达和活性的影响; 3） 表征激动剂诱导的P2受体脱敏，并评估 在脱敏作用的共识磷酸化位点在这些 受体;和4）通过克隆和表达其cDNA， HSG-PA唾液容量敏感性氯通道功能 细胞调节性容积减少（RVD），这是一个由P2 U增强的过程 受体激活 总之，这些研究将提供一个更全面的 认识P2受体在调节 唾液分泌和参与表达的因子， 这些受体的活性。 最终目标是阐明 唾液P2受体对维持口腔健康的贡献。

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.