METABOTROPIC GLUTAMATE RECEPTORS ARE INVOLVED IN THE DETECTION OF IMP AND L-AMINO ACIDS BY MOUSE TASTE SENSORY CELLS
METABOTROPIC GLUTAMATE RECEPTORS ARE INVOLVED IN THE DETECTION OF IMP AND L-AMINO ACIDS BY MOUSE TASTE SENSORY CELLS
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DOI：
10.1016/j.neuroscience.2015.12.008
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发表时间：
2016-03-01
期刊：
影响因子：
3.3
通讯作者：
Delay, E. R.
中科院分区：
文献类型：
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作者：
Choudhuri, S. Pal;Delay, R. J.;Delay, E. R.
G 蛋白偶联受体被认为参与鲜味和 L-氨基酸味道的检测。这些包括异二聚体味觉受体 1 型成员 1 (T1r1) + 味觉受体 1 型成员 3 (T1r3)、mGluR4 和 mGluR1 的味觉和大脑变体以及钙传感器。虽然一些研究表明 T1r1 + T1r3 是一种广泛调节的 L-氨基酸受体，但人们对代谢型谷氨酸受体 (mGluR) 在 L-氨基酸味觉转导中的功能知之甚少。使用比率染料 Fura 2 AM 对 T1r3-GFP 和 T1r3 敲除 (T1r3 KO) 小鼠的分离味觉感觉细胞 (TSC) 进行钙成像，以研究不同 mGluR 在检测各种 L-氨基酸和肌苷 5' 单磷酸 (IMP) 中的作用。使用对各种 mGluR 具有选择性的激动剂，例如 (RS)-3,5-二羟基苯基甘氨酸 (DHPG)（一种 mGluR1 激动剂）和 L-(+)-2-氨基-4-磷酸丁酸 (L-AP4)（一种 mGluR4 激动剂），我们评估了 TSC，以确定它们是否可能对这些激动剂、IMP 和三种 L-氨基酸（单钾）做出反应。 L-谷氨酸、L-丝氨酸和L-精氨酸）。此外，我们使用针对不同 mGluR 的选择性拮抗剂，例如 (RS)-1-氨基茚满-1,5-二羧酸 (AIDA)（一种 mGluR1 拮抗剂）和 (RS)-α-甲基丝氨酸-O-磷酸 (MSOP)（一种 mGluR4 拮抗剂），以确定它们是否可以阻断这些 L-氨基酸和 IMP 引发的反应。我们发现 L-氨基酸和 IMP 反应细胞也对每种激动剂有反应。 mGluR4 和 mGluR1 的拮抗剂显着阻断 IMP 和每种 L-氨基酸引起的反应。总的来说，这些数据为 mGluR1 和 mGluR4 的味觉和大脑变异参与小鼠 L-氨基酸和 IMP 味觉反应提供了证据，并支持多个受体有助于 IMP 和 L-氨基酸味觉的概念。 (C) 2015 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
G-protein-coupled receptors are thought to be involved in the detection of umami and L-amino acid taste. These include the heterodimer taste receptor type 1 member 1 (T1r1) + taste receptor type 1 member 3 (T1r3), taste and brain variants of mGluR4 and mGluR1, and calcium sensors. While several studies suggest T1r1 + T1r3 is a broadly tuned L-amino acid receptor, little is known about the function of metabotropic glutamate receptors (mGluRs) in L-amino acid taste transduction. Calcium imaging of isolated taste sensory cells (TSCs) of T1r3-GFP and T1r3 knock-out (T1r3 KO) mice was performed using the ratiometric dye Fura 2 AM to investigate the role of different mGluRs in detecting various L-amino acids and inosine 5' monophosphate (IMP). Using agonists selective for various mGluRs such as (RS)-3,5-dihydroxyphenylglycine (DHPG) (an mGluR1 agonist) and L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) (an mGluR4 agonist), we evaluated TSCs to determine if they might respond to these agonists, IMP, and three L-amino acids (monopotassium L-glutamate, L-serine and L-arginine). Additionally, we used selective antagonists against different mGluRs such as (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) (an mGluR1 antagonist), and (RS)-alpha-methylserine-O-phosphate (MSOP) (an mGluR4 antagonist) to determine if they can block responses elicited by these L-amino acids and IMP. We found that L-amino acid- and IMP-responsive cells also responded to each agonist. Antagonists for mGluR4 and mGluR1 significantly blocked the responses elicited by IMP and each of the L-amino acids. Collectively, these data provide evidence for the involvement of taste and brain variants of mGluR1 and mGluR4 in L-amino acid and IMP taste responses in mice, and support the concept that multiple receptors contribute to IMP and L-amino acid taste. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.