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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）：主要的味觉（甜、酸、苦、咸和鲜味）通常与不同类型的食物有关。例如，鲜味通常是富含蛋白质和某些L-氨基酸的食物的信号。然而，这些感觉的基础是有争议的，也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T1 R1/T1 R3，它可以检测到鲜味刺激，包括谷氨酸和更多的L-氨基酸。相比之下，其他分子和行为研究报告的证据表明，L-AP 4（一种有效的mGluR 4激动剂）激发传入信号，模拟鲜味刺激，表明味觉mGluR 4受体参与鲜味。这一争议是由缺乏T1 R3的小鼠的研究引发的。一项研究报道T1 R3敲除小鼠完全消除了鲜味（Zhao et al.，2003），而另一项用独立开发的T1 R3敲除小鼠的研究仅报道了鲜味的减少（Damak et al.，2003年）。用从Damak等人获得的T1 R3敲除小鼠进行的初步阈值实验发现，这些小鼠几乎可以与相同遗传背景的野生型小鼠一样品尝谷氨酸。此外，对大鼠的初步研究表明，mGluR 4拮抗剂改变了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，沿着其他研究，表明T1 R3以外的受体有助于鲜味。本提案中的两个具体目标将测试某些L-氨基酸（例如，L-谷氨酸）通过两种受体（T1 R1/T1 R3，味觉-mGluR 4）和其他L-氨基酸（例如，L-精氨酸）由一种受体（T1 R1/T1 R3）检测。具体目标1将通过评估：a）这些物质的味觉阈值，B）使用条件性味觉厌恶方法在这些物质之间的感知相似性，以及c）使用辨别方法在这些物质之间的感知差异，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T1 R3敲除小鼠中的味觉品质的相似程度。具体目标2将使用相同的行为方法在野生型和T1 R3敲除小鼠中检查mGluR 4拮抗剂对这些氨基酸的味道质量的影响。从这些敲除和野生型小鼠实验中开发的行为特征将为T1 R3和taste-mGluR 4受体在这些氨基酸的传入信号传导中的作用提供新的见解。对这些味觉传导机制的理解在应用于营养不良个体的食物摄入调节时可以具有巨大的健康护理意义（例如，糖尿病、心血管疾病、老年人）。