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Br J Pharmacol. 1999 Nov;128(5):1027-34. doi: 10.1038/sj.bjp.0702885.
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Behavioral responses to glutamate receptor agonists and antagonists implicate the involvement of brain-expressed mGluR4 and mGluR1 in taste transduction for umami in mice.行为反应谷氨酸受体激动剂和拮抗剂暗示了脑表达的 mGluR4 和 mGluR1 在味觉转导鲜味中的参与。
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本文引用的文献

1
Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor.配体与代谢型谷氨酸受体mGluR4亚型的氨基末端结构域结合。
J Biol Chem. 1999 Apr 9;274(15):10008-13. doi: 10.1074/jbc.274.15.10008.
2
Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity.假定的哺乳动物味觉受体：一类具有独特拓扑选择性的味觉特异性G蛋白偶联受体。
Cell. 1999 Feb 19;96(4):541-51. doi: 10.1016/s0092-8674(00)80658-3.
3
LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors.LY341495是一种对II型代谢型谷氨酸受体具有纳摩尔级效力和选择性的拮抗剂。
Neuropharmacology. 1998;37(1):1-12. doi: 10.1016/s0028-3908(97)00191-3.
4
A [35S]GTPgammaS binding assessment of metabotropic glutamate receptor standards in Chinese hamster ovary cell lines expressing the human metabotropic receptor subtypes 2 and 4.在表达人类代谢型谷氨酸受体亚型2和4的中国仓鼠卵巢细胞系中对代谢型谷氨酸受体标准品进行[35S]GTPγS结合评估。
Neuropharmacology. 1998;37(2):179-87. doi: 10.1016/s0028-3908(98)00011-2.
5
Characterization and solubilization of bitter-responsive receptors that couple to gustducin.与味觉传导素偶联的苦味反应受体的表征与增溶
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8933-8. doi: 10.1073/pnas.95.15.8933.
6
Reduction of sensory and metabotropic glutamate receptor responses in the thalamus by the novel metabotropic glutamate receptor-1-selective antagonist S-2-methyl-4-carboxy-phenylglycine.新型代谢型谷氨酸受体-1选择性拮抗剂S-2-甲基-4-羧基苯甘氨酸对丘脑感觉性和代谢型谷氨酸受体反应的抑制作用
Neuroscience. 1998 Aug;85(3):655-8. doi: 10.1016/s0306-4522(98)00048-7.
7
Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells.Ⅲ组人代谢型谷氨酸受体4、7和8：分子克隆、功能表达及在RGT细胞中的药理学特性比较
Brain Res Mol Brain Res. 1998 Jan;53(1-2):88-97. doi: 10.1016/s0169-328x(97)00277-5.
8
N-acetylaspartylglutamate selectively activates mGluR3 receptors in transfected cells.N-乙酰天门冬氨酰谷氨酸在转染细胞中选择性激活代谢型谷氨酸受体3（mGluR3）。
J Neurochem. 1997 Jul;69(1):174-81. doi: 10.1046/j.1471-4159.1997.69010174.x.
9
(RS)-2-chloro-5-hydroxyphenylglycine (CHPG) activates mGlu5, but no mGlu1, receptors expressed in CHO cells and potentiates NMDA responses in the hippocampus.（RS）-2-氯-5-羟基苯甘氨酸（CHPG）可激活在CHO细胞中表达的代谢型谷氨酸受体5（mGlu5），但不激活代谢型谷氨酸受体1（mGlu1），并增强海马体中的N-甲基-D-天冬氨酸（NMDA）反应。
Neuropharmacology. 1997 Feb;36(2):265-7. doi: 10.1016/s0028-3908(97)00001-4.
10
Cloning and characterization of a metabotropic glutamate receptor, mGluR4b.一种代谢型谷氨酸受体mGluR4b的克隆与特性分析
Neuropharmacology. 1997 Jan;36(1):21-30. doi: 10.1016/s0028-3908(96)00153-0.

鲜味肽对大鼠mGlu4a受体配体结合及功能的影响可能表明该受体参与了谷氨酸钠味觉转导。

Effect of the umami peptides on the ligand binding and function of rat mGlu4a receptor might implicate this receptor in the monosodium glutamate taste transduction.

作者信息

Monastyrskaia K, Lundstrom K, Plahl D, Acuna G, Schweitzer C, Malherbe P, Mutel V

机构信息

Pharma Division Preclinical CNS Research Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland.

出版信息

Br J Pharmacol. 1999 Nov;128(5):1027-34. doi: 10.1038/sj.bjp.0702885.

DOI:10.1038/sj.bjp.0702885
PMID:10556940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1571727/
Abstract
  1. The effect of several metabotropic ligands and di- or tripeptides were tested on the binding of [3H]-L(+)-2-amino-4-phosphonobutyric acid ([3H]-L-AP4) on rat mGlu4 receptor. For selected compounds, the functional activity was determined on this receptor using the guanosine-5'[gamma-35S]-thiotriphosphate [gamma-35S]-GTP binding assay. 2. Using the scintillation proximity assay, [3H]-L-AP4 saturation analysis gave binding parameters K(D) and Bmax values of 150 nM and 9.3 pmoles mg-1 protein, respectively. The specific binding was inhibited concentration-dependently by several mGlu receptor ligands, and their rank order of affinity was established. 3. Several peptides inhibited the [3H]-L-AP4 binding with the following rank order of potency: glutamate-glutamate>glutamate-glutamate-leucine=aspartate - glutamate>>glutamate - glutamate-aspartate>lactoyl-glutamate>>aspartate-aspartate. Aspartate-phenylalanine-methyl ester (aspartame) was inactive up to 1 mM and guanosine-5'-monophosphate and inosine-5'-monophosphate were inactive up to 100 micronM. 4. The [gamma-35S]-GTP binding functional assay was used to determine the agonist activities of the different compounds. For the rat mGlu4 agonists, L-AP4 and L-glutamate, the correlation between their occupancy and activation of the receptor was close to one. The peptides, Glu-Glu, Asp-Glu and Glu-Glu-Asp failed to stimulate the [gamma-35S]-GTP binding at receptor occupancy greater than 80% and Glu-Glu-Leu appeared to be a weak partial agonist. These peptides did not elicit a clear dose-dependent umami perception. However, Glu-lac showed a good correlation between its potency to stimulate the [gamma-35S]-GTP binding and its affinity for displacement of [3H]-L-AP4 binding. These data are in agreement with the peptide taste assessment in human subjects, which showed that the acid derivatives of glutamate had characteristics similar to umami.
摘要
  1. 测试了几种促代谢型配体和二肽或三肽对[3H]-L(+)-2-氨基-4-膦酰丁酸（[3H]-L-AP4）与大鼠mGlu4受体结合的影响。对于选定的化合物，使用鸟苷-5'[γ-35S]-硫代三磷酸（[γ-35S]-GTP）结合试验测定其在该受体上的功能活性。2. 使用闪烁邻近分析，[3H]-L-AP4饱和分析得出结合参数K(D)和Bmax值分别为150 nM和9.3 pmol/mg蛋白质。几种mGlu受体配体浓度依赖性地抑制特异性结合，并确定了它们的亲和力顺序。3. 几种肽以以下效力顺序抑制[3H]-L-AP4结合：谷氨酸-谷氨酸>谷氨酸-谷氨酸-亮氨酸=天冬氨酸-谷氨酸>>谷氨酸-谷氨酸-天冬氨酸>乳酰谷氨酸>>天冬氨酸-天冬氨酸。天冬氨酸-苯丙氨酸甲酯（阿斯巴甜）在高达1 mM时无活性，鸟苷-5'-单磷酸和肌苷-5'-单磷酸在高达100 μM时无活性。4. 使用[γ-35S]-GTP结合功能试验测定不同化合物的激动剂活性。对于大鼠mGlu4激动剂L-AP4和L-谷氨酸，它们对受体的占据与激活之间的相关性接近1。肽Glu-Glu、Asp-Glu和Glu-Glu-Asp在受体占据率大于80%时未能刺激[γ-35S]-GTP结合，而Glu-Glu-Leu似乎是一种弱部分激动剂。这些肽未引发明确的剂量依赖性鲜味感知。然而，Glu-lac在刺激[γ-35S]-GTP结合的效力与其对[3H]-L-AP4结合置换的亲和力之间显示出良好的相关性。这些数据与人体受试者的肽味觉评估一致，该评估表明谷氨酸的酸性衍生物具有类似于鲜味的特征。