Human and rat T1R1/T1R3 recognize umami taste stimuli. (A) mGluR1 residues (PDB entry no. 1EWK) that contact the l-glutamate side chain carboxylate are shown in red, and residues that contact the l-glutamate α-amino acid moiety are shown in green. (B) Gα15 cells transiently transfected with human T1R1 and T1R3 were assayed for intracellular calcium increases in response to increasing concentrations of l-glutamate in the presence or absence of 1 mM IMP. Each imaged field shown contains ≈1,000 confluent cells. (C) Human T1R1/T1R3 dose responses were determined for l-glutamate in the presence and absence of 0.2 mM IMP. Dose responses were normalized to the maximal percentage of responding cells, which was ≈5% for l-glutamate and ≈10% for l-glutamate plus IMP. Values represent the mean ± SE of four independent responses. The x axis circles represent average psychophysical detection threshold values for l-glutamate in the presence and absence of 0.2 mM IMP. (D) Human T1R1/T1R3 responses to 25 mM d-glutamate, 25 mM l-glutamate, 25 mM l-aspartate, 25 mM l-AP4, and binary mixtures of these compounds with 2.5 mM IMP, 2.5 mM GMP, or 2.5 mM CMP were determined. (E) Human T1R1/T1R3 dose responses were determined for IMP in the presence of 0.2 and 2 mM l-glutamate and normalized to the maximal percentages of responding cells, which were ≈10%. Values represent the mean ± SE of four independent responses. (F) Human T1R2/T1R3 responses to 25 mM l-glutamate, 100 mM sucrose (SUC), 2.5 mM d-tryptophan, 1.5 mM aspartame (ASP), and 0.4 mM saccharin (SAC) were determined in the presence and absence of 2.5 mM IMP. (G) Human T1R1/T1R3 dose responses were determined for l-aspartate and l-AP4 in the presence of 0.2 mM IMP. Dose responses were normalized to the maximal percentage of responding cells, which was ≈5% for l-aspartate plus IMP and ≈10% for l-AP4 plus IMP. Values represent the mean ± SE of four independent responses. The x axis circles represent average psychophysical detection threshold values for l-aspartate plus 0.2 mM IMP and l-AP4 plus 0.2 mM IMP. (H) Human T1R1/T1R3 responses to sucrose (100 mM), d-tryptophan (20 mM), aspartame (2 mM), saccharin (1 mM), l-tyrosine (5 mM), and d-glutamate, l-glutamine, d-aspartate, glycine, l-histidine, l-leucine, l-lysine, l-proline, and l-serine (each at 10 mM) were determined in the presence and absence of 1 mM IMP. (I) HEK-293T cells were transiently transfected with rat T1R1, rat T1R3, and Gα15/i1 and assayed for increases in intracellular calcium in response to 25 mM d-glutamate, 25 mM l-glutamate, 25 mM l-aspartate, 25 mM l-AP4, and binary mixtures with 2.5 mM IMP, 2.5 mM GMP, or 2.5 mM CMP. (J) Rat T1R1/T1R3 dose responses were determined for l-aspartate and l-glutamate in the presence of 0.2 mM IMP. Dose responses were normalized to the maximal percentage of responding cells, which was ≈10% for l-aspartate plus IMP and ≈15% for l-glutamate plus IMP. Values represent the mean ± SE of four independent responses. The activities in D, F, H, and I represent the mean ± SE number of responding cells for four imaged fields of ≈1,000 confluent cells.