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 |
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Authors: | Monastyrskaia K Lundstrom K Plahl D Acuna G Schweitzer C Malherbe P Mutel V |
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Institution: | Pharma Division Preclinical CNS Research Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland. |
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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. |
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