Rapid Throughput Concentration-Response Analysis of Human Taste Discrimination

Abstract

Human taste threshold measurements often are used to infer tastant receptor functionality.However, taste thresholds can be influenced by receptor-independent variables. Examination of the full range of taste-active concentrations by taste discrimination has been hampered by logistics of testing multiple concentrations in replicate with human subjects. We developed an automated rapid throughput operant methodology for taste discrimination and applied it to concentration-response analysis of human taste. Tastant solutions (200 µl) drawn from a 96well plate and self-administered to the tongue served as discriminative stimuli for moneyreinforced responses on a touch-sensitive display. Robust concentration-response functions for "basic taste" stimuli were established, with particular focus on agonists of the TAS1R2/R3 receptor. With a training cue of 100 mM sucrose, EC50s of 56 µM, 79 µM, 310 µM, and 40 mM were obtained for rebaudioside A, sucralose, acesulfame potassium, and sucrose, respectively.Changing the sucrose training cue to 300 mM had no impact but changing to 30 mM resulted in slight leftward shifts in potencies. A signal detection method also was used to determine values of d', a probabilistic value for discriminability, which indicated that 5 mM was near the limits of detection for sucrose. With repeated testing, both EC50s and 5 mM sucrose d' values were established for each individual subject. The results showed little correspondence between threshold sensitivities and EC50 values for sucrose. We conclude that concentration-response analysis of taste discrimination provides a more reliable means of inferring receptor function than measurement of discriminability at the lowest detectable tastant concentrations. SIGNIFICANCE STATEMENTMany inferences about human tastant receptor functionality have been made from taste threshold measurements, which can be influenced by variables unrelated to receptors. We herein report a new methodology that enables rigorous concentration-response analysis of human taste discrimination, and its use toward quantitative characterization of tastant agonist This article has not been copyedited and formatted. The final version may differ from this version.

Biohybrid Tongue for Evaluation of Taste Interaction between Sweetness and Sourness

“…Further, we calculated the area under the curve (AUC) in Figure B to obtain the energy of oscillations stimulated and drew the dose-dependent curve, as shown in Figure D. According to the nonlinear regression analysis, the fitting curve was in good agreement with the theoretical psychophysiological curve of the taste system, and the EC50 was calculated to be 1.41% (41 mM), which agreed with the results obtained from the sensory evaluation …”

“…Cooperativity as indicated could result from agonist–receptor interactions. After the acceleration, taste discrimination concentration–response functions for sucrose and citric acid are all saturated, as would be expected of a receptor-mediated process …”

“…According to the nonlinear regression analysis, the fitting curve was in good agreement with the theoretical psychophysiological curve of the taste system, and the EC50 was calculated to be 1.41% (41 mM), which agreed with the results obtained from the sensory evaluation. 29 3.4. Taste Detection and Evaluation of the Biohybrid Tongue for Acidulant.…”

A Dynamic Mass Redistribution Assay for the Human Sweet Taste Receptor Uncovers G-Protein Dependent Biased Ligands

“…Effects were dose-dependent and could not be detected on the parental cell lines at concentrations up to 1–2 mM. EC 50 values confirmed that, overall, agonists activated the sweet taste receptor with the expected rank order of potency based on human taste data ( Schiffman and Gatlin, 1993 ; Li and Servant, 2008 ; Palmer et al, 2021 ). At concentrations ≥3 mM, we could detect receptor independent positive DMR responses.…”

Human Oral Sensitivity to and Taste Modulation by 3-Mercapto-2-Methylpentan-1-ol

“…Measured taste sensitivity tends to be higher with larger volumes, though this effect is relatively small and most pronounced at volumes substantially less than 1 ml (O'Mahony et al 1982;O'Mahony et al 1984, Brosvic andMcLaughlin 1989). Furthermore, reliable taste judgments are possible even with a small fraction of 1 ml (Colvin et al 2018;Palmer et al 2021). However, the effect of volume on judgments of retronasal aroma have not been explored as thoroughly, so some results might differ if more natural volumes were used.…”