AGONISTS/ANTAGONISTS FOR CHARACTERIZING CHEMORECEPTORS

味觉和嗅觉与食物密切相关 选择、鉴定、消化和代谢，以及在 复制(嗅觉)与一般的意识和欣赏 对环境的影响。这些感官功能的丧失或改变 可能会导致营养方面的妥协，并导致 生活质量。我们工作的总体目标是 在分子水平上理解这些感官，所以 针对这些感觉缺陷的治疗方法可以从 知识和理性的基础。目前的研究提案 重点生产拮抗剂和激动剂，以镇静和 嗅觉感受器，以及这些感受器在表征 受体结合蛋白。生物化学技术， 神经生理学、合成有机化学和细胞培养 是用于解决以下问题的集成协作方法的核心 这项工作的目的。我们的实验模型，鲶鱼，我。 斑点鱼，具有独特的和可识别的受体 化学促进剂氨基酸。这一模式已被证明是有价值的。 了解味觉和嗅觉的基本机制。 这项提议的具体目标是：(1)确定小说 味觉和嗅觉受体的激动剂和拮抗剂形成三种 主要分子类-氨基酸类似物(包括 光亲和探针)、单抗和凝集素；(2) 描述这些激动剂的特征。使用神经生理学的拮抗剂 和生化结合分析，定义了它们的特异性、模式 作用和抑制动力学；以及(3)在 在接收和转导以及标记中表征事件 经电泳法鉴定受体蛋白。这些 目标将通过一系列实验来实现 强调多学科方法的程序。专一性， 使用这两种方法研究了作用模式和抑制类型 患者的刺激效果和交叉适应程序 生物化学中的神经生理学检测和竞争结合 化验。所得到的表征探针和竞争结合 在生化分析中。然后将所得到表征探针 用来定义受体的亚基和选择性。未来 研究将强调使用这些证明来提纯和 在原位定位受体蛋白--完成此操作后 研究，我们将生产出化学探针的必要性 受体的鉴定、纯化和记录，并具有 实现了对受体机制的更全面的了解 在味觉和嗅觉上。

The senses of taste and olfaction are intimately involved in food selection, identification digestion and metabolism, as well as in reproduction (olfaction) and the general awareness and appreciation of the environment. Loss or alteration in function of these senses can lead to a nutritional compromises and to a decrease in the quality of life. The overall goal of our work has been the understanding of these senses at the molecular level, so that therapies for deficiencies of these sense may be approached from knowledgeable and rational bases. The current research proposal emphasizes production of antagonists and agonist to qustatory and olfactory receptors, and the use of these in characterizing the receptor binding proteins. The techniques of biochemistry, neurophysiology, synthetic organic chemistry and cell culture are central to the integrated collaborative approaches used to address the aims of this work. Our experimental model, the catfish, I. punctatus, possesses unique and identifiable receptors for various chemostimualtrou amino acids. This model has proved invalualboej to understanding the fundamental mechanisms of taste and olfaction. The specific aims of this proposal seek to (1) identify novel agonist and antagonists to taste and olfactory receptors form three major molecular classes - amino acid analogy (including photoaffinity probes), monoclonal antibodies and lectins; (2) characterize these agonist. antagonists using neurophysiological and biochemical binding assays, defining their specificity, mode of action and inhibitory kinetic; and (3) utilize these parve in characterizing events in reception and transduction and in labeling and identifying receptor proteins after electrophoresis. These aims will be accomplished through a series of experimental procedures that emphasize multidisiplinary approach. Specificity, mode of action and type of inhibition are studied using both stimulatory effectiveness and cross-adaptation procedures in a neurophysiological assay and competitive binding in biochemical assays. The resultant characterized probes and competitive binding in biochemical assays. The resultant characterized probe are then used to define the receptors as to subcalsand selectivity. Future studies will emphasize use of these proves in purifying and localizing receptors proteins in situ-upon completion of this study, we will have produced the chemical probes necessity for receptor identification, purification and documentation, and have achieved a more complete understanding of the receptor mechanisms in taste and olfaction.