BIOCHEMICAL MECHANISMS OF TASTE FUNCTION

味觉与食物的选择密切相关， 识别、消化和新陈代谢。本文件的遗失或更改 化学感觉可导致营养和新陈代谢妥协，并导致 生活质量下降。我们工作的总目标是寻求一个 对味觉感受器分子生化事件的理解 细胞水平，因此味觉缺陷的治疗可以 在知识和理性的基础上进行接触。目前的提案 强调一种研究方法，以允许对 受体，味觉和蛋白质转导序列的评估 味觉受体的纯化。这个实验模型是一种名为I.marktatus的模型， 拥有独特、高度敏感和可识别的受体，可识别各种 化学刺激性氨基酸。该模型已被证明是非常有价值的 了解味觉和嗅觉的基本机制。这个 本提案的具体目的是：1)描述 通过使用新的受体结合技术来确定味觉受体位置 这些受体的可用激动剂/拮抗剂；2)研究 鉴定第二信使形成酶的转导序列 系统(包括腺苷和鸟苷环化酶、磷脂酶C和 磷脂酶A2)，并通过研究重组的味觉刺激- 味觉细胞激活的(配体门控)阳离子通道；3) 表征受体通过GTP与第二信使形成的联系 结合调节蛋白；以及4)提纯和表征这些味道 感受器。这些目标将通过使用生化和 神经生理学方法。受体大分子的知识。的 特别令人感兴趣的是最近的观察表明，在这两个 这种动物的主要味觉感受器通路，显然是通过 第二信使的产生，另一种是通过配体门控阳离子 受体。拟议的研究将允许对这些问题进行详细检查 我们假设的两种机制在哺乳动物身上也是活跃的。 受体系统。在完成这些研究后，我们将拥有 评估受体药理学，确定其相对重要性 几种第二信使和转导系统的味道及纯化 重组状态下用于研究的味觉受体蛋白。

The sense of taste is intimately involved in food selection, identification, digestion and metabolism. Loss or alteration of this chemo-sense can lead to nutritional and metabolic compromises and to a decrease in the quality of life. The overall goals of our work seek an understanding of the molecular-biochemical events at the taste receptor cell level so that therapies for deficiencies in the sense of taste can be approached from knowledgeable and rational basis. The current proposal emphasizes a research approach to allow characterization of the receptors, evaluation of the transduction sequences in taste and purification of taste receptors. The experimental model, I. punctatus, possesses unique, highly sensitive and identifiable receptors for various chemostimulatory amino acids. This model has proved very valuable in understanding the fundamental mechanisms of taste and olfaction. The specific aims of this proposal seek to 1) describe the pharmacology of taste receptor sites through receptor binding techniques using newly available agonists/antagonists to these receptors; 2) investigate the transduction sequences by characterizing second messenger-forming enzyme systems (including adenylate and guanylate cyclase, phospholipase C and phospholipase A2) and by studying the reconstituted taste stimulus- activated (ligand-gated) cation channels from taste cells; 3) characterize the receptor link to second messenger formation via GTP- binding regulatory proteins; and 4) purify and characterize these taste receptors. These aims will be accomplished using both biochemical and neurophysiological approaches. Knowledge of receptor macromolecules. Of particular interest are recent observations indicating that, of the two main taste receptor pathways i this animal, one apparently operates via production of second messengers, the other via a ligand-gated cation receptor. The proposed studies will allow a detailed examination of these two mechanisms, ones which we hypothesize are also active in mammalian receptor systems. Upon completion of these studies, we will have evaluated receptor pharmacology, determined the relative importance to taste of several second messenger and transduction systems and purified taste receptor proteins for study in the reconstituted state.