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

1 The effect of several metabotropic ligands and di- or tripeptides were te sted on the binding of [H-3]-L(+)-2-amino-4-phosphonobutyric acid ([H-3]-L- AP4) on rat mGlu(4) receptor. For selected compounds, the functional activi ty was determined on this receptor using the guanosine-5'[gamma-S-35]-thiot riphosphate [gamma-S-35]-GTP binding assay. 2 Using the scintillation proximity assay, [H-3]-L-AP4 saturation analysis gave binding parameters K-D and B-max values of 150 nM and 9.3 pmoles mg(-1 ) protein, respectively. The specific binding was inhibited concentration-d ependently by several mGlu receptor ligands, and their rank order of affini ty was established. 3 Several peptides inhibited the [H-3]-L-AP4 binding with the following ran k order of potency: glutamate-glutamate > glutamate-glutamate-leucine = asp artate - glutamate, > > glutamate - glutamate-aspartate > lactoyl-glutamate > > aspartate-aspartate. Aspartate-phenylalanine-methyl eater (aspartame) was inactive up to 1 mM and guanosine-5'-monophosphate and inosine-5'-monop hosphate were inactive up to 100 mu M. 4 The [gamma-S-35]-GTP binding functional assay was used to determine the a gonist activities of the different compounds. For the rat mGlu(4) agonists, L-AP4 and L-glutamate, the correlation between their occupancy and activat ion of the receptor was close to one. The peptides, Glu-Glu, Asp-Glu and Gl u-Glu-Asp failed to stimulate the [gamma-S-35]-GTP binding at receptor occu pancy greater than 80% and Glu-Glu-Leu appeared to be a weak partial agonis t. These peptides did not elicit a clear dose-dependent umami perception. H owever, Glu-lac showed a good correlation between its potency to stimulate the [gamma-S-35]-GTP binding and its affinity for displacement of [H-3]-L-A P4 binding. These data are in agreement with the peptide taste assessment i n human subjects, which showed that the acid derivatives of glutamate had c haracteristics similar to umami.