Yasumatsu Keiko, Manabe Tomohiro, Yoshida Ryusuke, Iwatsuki Ken, Uneyama Hisayuki, Takahashi Ichiro, Ninomiya Yuzo
Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Division of Sensory Physiology, Research and Development Center for Taste and Odor Sensing, Kyushu University, Fukuoka, Japan.
J Physiol. 2015 Feb 15;593(4):1021-34. doi: 10.1113/jphysiol.2014.284703. Epub 2015 Jan 22.
The taste receptor T1R1 + T1R3 heterodimer and metabotropic glutamate receptors (mGluR) may function as umami taste receptors. Here, we used mGluR4 knockout (mGluR4-KO) mice and examined the function of mGluR4 in peripheral taste responses of mice. The mGluR4-KO mice showed reduced responses to glutamate and L-AP4 (mGluR4 agonist) in the chorda tympani and glossopharyngeal nerves without affecting responses to other taste stimuli. Residual glutamate responses in mGluR4-KO mice were suppressed by gurmarin (T1R3 blocker) and AIDA (group I mGluR antagonist). The present study not only provided functional evidence for the involvement of mGluR4 in umami taste responses, but also suggested contributions of T1R1 + T1R3 and mGluR1 receptors in glutamate responses.
Umami taste is elicited by L-glutamate and some other amino acids and is thought to be initiated by G-protein-coupled receptors. Proposed umami receptors include heterodimers of taste receptor type 1, members 1 and 3 (T1R1 + T1R3), and metabotropic glutamate receptors 1 and 4 (mGluR1 and mGluR4). Accumulated evidences support the involvement of T1R1 + T1R3 in umami responses in mice. However, little is known about the in vivo function of mGluR in umami taste. Here, we examined taste responses of the chorda tympani (CT) and the glossopharyngeal (GL) nerves in wild-type mice and mice genetically lacking mGluR4 (mGluR4-KO). Our results indicated that compared to wild-type mice, mGluR4-KO mice showed significantly smaller gustatory nerve responses to glutamate and L-(+)-2-amino-4-phosphonobutyrate (an agonist for group III mGluR) in both the CT and GL nerves without affecting responses to other taste stimuli. Residual glutamate responses in mGluR4-KO mice were not affected by (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (an antagonist for group III mGluR), but were suppressed by gurmarin (a T1R3 blocker) in the CT and (RS)-1-aminoindan-1,5-dicarboxylic acid (an antagonist for group I mGluR) in the CT and GL nerve. In wild-type mice, both quisqualic acid (an agonist for group I mGluR) and L-(+)-2-amino-4-phosphonobutyrate elicited gustatory nerve responses and these responses were suppressed by addition of (RS)-1-aminoindan-1,5-dicarboxylic acid and (RS)-alpha-cyclopropyl-4-phosphonophenylglycine, respectively. Collectively, the present study provided functional evidences for the involvement of mGluR4 in umami taste responses in mice. The results also suggest that T1R1 + T1R3 and mGluR1 are involved in umami taste responses in mice. Thus, umami taste would be mediated by multiple receptors.
味觉受体T1R1 + T1R3异二聚体和代谢型谷氨酸受体（mGluR）可能作为鲜味味觉受体发挥作用。在此，我们使用mGluR4基因敲除（mGluR4-KO）小鼠，研究了mGluR4在小鼠外周味觉反应中的功能。mGluR4-KO小鼠对鼓索神经和舌咽神经中的谷氨酸和L-AP4（mGluR4激动剂）的反应降低，而不影响对其他味觉刺激的反应。mGluR4-KO小鼠中残留的谷氨酸反应被匙羹藤酸（T1R3阻断剂）和艾达（I组mGluR拮抗剂）抑制。本研究不仅为mGluR4参与鲜味味觉反应提供了功能证据，还表明T1R1 + T1R3和mGluR1受体在谷氨酸反应中的作用。
鲜味味觉由L-谷氨酸和其他一些氨基酸引发，被认为是由G蛋白偶联受体启动的。提议的鲜味受体包括味觉受体1型成员1和3的异二聚体（T1R1 + T1R3）以及代谢型谷氨酸受体1和4（mGluR1和mGluR4）。越来越多的证据支持T1R1 + T1R3参与小鼠的鲜味反应。然而，关于mGluR在鲜味味觉中的体内功能知之甚少。在此，我们检测了野生型小鼠和基因缺失mGluR4的小鼠（mGluR4-KO）的鼓索神经（CT）和舌咽神经（GL）的味觉反应。我们的结果表明，与野生型小鼠相比，mGluR4-KO小鼠对CT和GL神经中的谷氨酸和L-(+)-2-氨基-4-膦酰丁酸（III组mGluR的激动剂）的味觉神经反应明显较小，而不影响对其他味觉刺激的反应。mGluR4-KO小鼠中残留的谷氨酸反应不受（RS）-α-环丙基-4-膦酰苯基甘氨酸（III组mGluR拮抗剂）的影响，但在CT中被匙羹藤酸（T1R3阻断剂）以及在CT和GL神经中被（RS）-1-氨基茚-1,5-二羧酸（I组mGluR拮抗剂）抑制。在野生型小鼠中，喹啉酸（I组mGluR激动剂）和L-(+)-2-氨基-4-膦酰丁酸均引发味觉神经反应，并且这些反应分别被添加的（RS）-1-氨基茚-1,5-二羧酸和（RS）-α-环丙基-4-膦酰苯基甘氨酸抑制。总体而言，本研究为mGluR4参与小鼠鲜味味觉反应提供了功能证据。结果还表明T1R1 + T1R3和mGluR1参与小鼠鲜味味觉反应。因此，鲜味味觉可能由多种受体介导。
