Taste Transduction and its Regulation

描述(申请人提供)：味觉系统的主要作用之一是识别有机体生存所需的营养物质。历史上，味觉系统一直被认为是僵化的，只报告味觉刺激的存在。然而，最近的证据表明，味觉系统可能受到许多激素的调节，这些激素可能会改变参与营养味觉转导的元素的表达和/或功能。拟议研究的主要目标是探索味觉系统对调节提示的反应能力，如激素，这些提示可能通过作用于特定的转导元件来调节外周味觉系统。该项目的一个目标是进一步确定参与大鼠味觉细胞中盐和水转导的通道。该项目的第一个目标将测试许多在其他盐分和水运输上皮细胞中表达的相同的离子通道和水通道在外周味觉系统中也表达的不对称。将使用分子生物学、免疫细胞化学和电生理技术来确定可能在盐和水转导途径中发挥作用的通道的表达和功能。这些包括与钠盐味觉有关的上皮性钠通道(ENaC)、CIC家族的氯通道以及囊性纤维化跨膜电导调节因子(CFTR)、水通道(AQP)水通道、内向整流钾通道ROMK1的鉴定和鉴定，所有这些都被初步数据证明存在于哺乳动物味觉细胞中。这项拟议研究的第二个目标将调查几种促钠激素(醛固酮、加压素和心钠素)调节这些已识别成分的表达和功能的能力。上述通道的一个共同特征是，它们受到一种或多种激素的调节，这些激素有助于维持上皮细胞运输过程中的盐分和水分平衡。我们将测试这一假设，即有助于味觉细胞中盐和水运输的转导元件对一种或多种调节其他上皮细胞中盐和水运输的钠激素做出反应。利用实时定量聚合酶链式反应和大鼠味觉细胞电生理记录，我们将检测这三种激素改变ENaC、CIC、CFTR、AQP和ROMK1的相对表达和功能的能力。综上所述，这些研究将有助于进一步阐明哺乳动物味觉细胞中盐和水的转导途径。此外，它应该提供一些最初的直接证据，证明味觉转导通路中的特定元素是否有能力受到激素信号的调节，并确定这种调节的机制。这些研究将试图提供直接证据，证明味觉系统是灵活的，并在帮助维持和恢复营养平衡方面发挥积极作用。

DESCRIPTION (provided by applicant): One of the main roles of the taste system is to identify nutrients an organism needs to survive. Historically, the taste system has been thought of as inflexible, merely reporting the presence of taste stimuli. However, recent evidence suggests that the taste system may be modulated by a number of hormones that may alter the expression and/or function of elements involved in nutrient taste transduction. The primary goal of the proposed studies is to explore the ability of the taste system to respond to regulatory cues, like hormones, that may modulate the peripheral gustatory system by acting on specific transduction elements. One goal of the project is to further identify channels that participate in salt and water transduction in rat taste cells. The first aim of the project will test the hyposthesis that many of the same ion channels and water channels that are expressed in other salt and water transporting epithelia are also expressed in the peripheral gustatory system. Molecular biological, immunocytochemical and electrophysiological techniques will be used to determine the expression and function of channels that may play roles in both salt and water transduction pathways. These include identification and characterization of the epithelial sodium channel (ENaC) involved in sodium salt taste, the chloride channels of the CIC family and the cystic fibrosis transmembrane conductance regulator (CFTR), aquaporin (AQP) water channels, the inward rectifying potassium channel, ROMK1, all that shown to be present in mammalian taste cells by preliminary data. The second goal of the proposed research will investigate the ability of several natriferic hormones (aldosterone, vasopressin and atrial natriuretic peptide) to modulate expression and function of these identified elements. A common feature of the aforementioned channels is that they are regulated by one or more of these hormones that maintain help salt and water balance in transporting epithelia. We will test the hypothesis that the transduction elements that contribute to salt and water transport in taste cells respond to one or more of the natriferic hormones that regulate salt and water movement in other epithelia. Using quantitative real-time PCR and electrophysiological recording in rat taste cells we will examine the ability of these three hormones to alter the relative expression and function of ENaC, CIC, CFTR, AQP and ROMK1. Taken together, these studies should help to further elucidate the transduction pathways for salts and water in mammalian taste cells. In addition, it should provide some of the first direct evidence as to the ability of specific elements in taste transduction pathways to be modulated by hormonal signals and to identify the mechanism underlying such modulation. These studies will attempt to provide direct evidence that the gustatory system is flexible and that it plays an active role in helping maintain and restore nutrient balance.