L-amino and acid taste in mice.

小鼠的 L-氨基酸和酸味。

基本信息

批准号：
6954830
负责人：
Eugene R Delay
金额：
$ 22.8万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-01 至 2008-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6954830
关键词：
alanine aminoacid arginine behavior test chemoreceptors genetically modified animals glutamate receptor glutamates laboratory mouse sensory mechanism taste taste threshold

项目摘要

DESCRIPTION (provided by applicant): Primary taste sensations (sweet, sour, bitter, salt, and umami) are often associated with different types of foods. For example, umami taste often signals food rich in proteins and certain L-amino acids. However, the basis of these sensations is controversial and not well understood. Molecular and limited behavioral studies have identified a candidate taste receptor, T1R1/T1R3, which detects umami stimuli, including monosodium glutamate, and many more L-amino acids. In contrast, other molecular and behavioral studies report evidence that L-AP4 (a potent mGluR4 agonist) elicits afferent signals that mimic umami stimulation, suggesting that a taste-mGluR4 receptor is involved in umami taste. This controversy is fueled by studies with mice lacking T1R3. One study reported that T1R3 knockout mice completely eliminated umami taste (Zhao et al., 2003), whereas another study with independently developed T1R3 knockout mice reported only a reduction in umami taste (Damak et al., 2003). Pilot threshold experiments with T1R3 knockout mice obtained from Damak et al. found that these mice can taste monosodium glutamate nearly as well as wild type mice of the same genetic background. In addition, preliminary studies with rats show that mGluR4 antagonists alter the taste of L-glutamate but have little effect on the taste of the amino acid L-arginine. These data, along with other studies, suggest that receptors other than T1R3 contribute to umami taste. Two Specific Aims in this proposal will test the hypothesis that some L-amino acids (e.g., L-glutamate) are detected by two receptors (T1R1/T1R3, taste-mGluR4) and other L-amino acids (e.g., L-arginine) are detected by one receptor (T1R1/T1R3). Specific Aim 1 will determine how similar the taste qualities of three L-amino acids (L-glutamate, L-arginine, and L-alanine) are in wild type and T1R3 knockout mice by assessing: a) taste thresholds for these substance, b) perceptual similarities between these substances using conditioned taste aversion methods, and c) perceptual differences between these substances using discrimination methods. Specific Aim 2 will examine the effects of mGluR4 antagonists on the taste qualities of these amino acids in wild type and T1R3 knockout mice using the same behavioral methods. The behavioral profiles developed from these experiments with knockout and wild-type mice will provide new insights into the roles of T1R3 and taste-mGluR4 receptors in afferent signaling of these amino acids. An understanding of these taste transduction mechanisms can have tremendous health care implications when applied to regulation of food intake by nutritionally challenged individuals (e.g., diabetics, cardiovascular disease, aged).

描述（由申请人提供）：主要味觉（甜、酸、苦、盐和鲜味）通常与不同类型的食物相关。例如，鲜味通常表明食物富含蛋白质和某些 L-氨基酸。然而，这些感觉的基础是有争议的，而且还没有得到很好的理解。分子和有限的行为研究已经确定了一种候选味觉受体 T1R1/T1R3，它可以检测鲜味刺激，包括谷氨酸钠和更多的 L-氨基酸。相比之下，其他分子和行为研究报告证据表明，L-AP4（一种有效的 mGluR4 激动剂）会引发模仿鲜味刺激的传入信号，这表明味觉 mGluR4 受体与鲜味有关。对缺乏 T1R3 的小鼠进行的研究加剧了这一争议。一项研究报告称，T1R3 基因敲除小鼠完全消除了鲜味（Zhao 等，2003），而另一项针对独立开发的 T1R3 基因敲除小鼠的研究报告称，鲜味仅减少（Damak 等，2003）。使用从 Damak 等人获得的 T1R3 敲除小鼠进行的试点阈值实验。发现这些小鼠几乎可以像具有相同遗传背景的野生型小鼠一样品尝味精。此外，对大鼠的初步研究表明，mGluR4拮抗剂会改变L-谷氨酸的味道，但对氨基酸L-精氨酸的味道几乎没有影响。这些数据与其他研究一起表明 T1R3 以外的受体有助于鲜味。该提案中的两个具体目标将检验以下假设：一些 L-氨基酸（例如，L-谷氨酸）由两种受体（T1R1/T1R3、味觉-mGluR4）和其他 L-氨基酸（例如，L-精氨酸）检测到。由一种受体 (T1R1/T1R3) 检测。具体目标 1 将通过评估以下各项来确定三种 L-氨基酸（L-谷氨酸、L-精氨酸和 L-丙氨酸）在野生型和 T1R3 敲除小鼠中的味道品质的相似程度：a) 这些物质的味觉阈值，b ) 使用条件味觉厌恶方法来确定这些物质之间的感知相似性，以及 c) 使用辨别方法来确定这些物质之间的感知差异。具体目标 2 将使用相同的行为方法检查 mGluR4 拮抗剂对野生型和 T1R3 敲除小鼠中这些氨基酸的味道质量的影响。通过这些基因敲除小鼠和野生型小鼠实验得出的行为特征将为了解 T1R3 和味觉 mGluR4 受体在这些氨基酸传入信号传导中的作用提供新的见解。当理解这些味觉传导机制应用于营养不良个体（例如糖尿病患者、心血管疾病患者、老年人）的食物摄入调节时，可以产生巨大的医疗保健意义。