‘Water-tastes’ are gustatory after-impressions elicited by water following the removal of a chemical solution from the mouth, akin to colour after-images appearing on ‘white’ paper after fixation on coloured images. Unlike colour after-images, gustatory after-effects are poorly understood1. One theory posits that ‘water-tastes’ are adaptation phenomena, in which adaptation to one taste solution causes the water presented subsequently to act as a taste stimulus2,3. An alternative hypothesis is that removal of the stimulus upon rinsing generates a receptor-based, positive, off-response in taste-receptor cells, ultimately inducing a gustatory perception4. Here we show that a sweet ‘water-taste’ is elicited when sweet-taste inhibitors are rinsed away. Responses of cultured cells expressing the human sweetener receptor directly parallel the psychophysical responses—water rinses remove the inhibitor from the heteromeric sweetener receptor TAS1R2–TAS1R3, which activates cells and results in the perception of strong sweetness from pure water. This ‘rebound’ activity occurs when equilibrium forces on the two-state allosteric sweet receptors result in their coordinated shift to the activated state upon being released from inhibition by rinsing5,6,7.
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The authors thank E. Chudoba, E. Schöley-Pohl and S. Demgensky for technical assistance. We thank G. Beauchamp, B. Cooperman and D. Krautwurst for comments and discussion. We are grateful to H. Schmale for the rat Tas1r3 cDNA and J. Slack for the HEK293T Gα16gust44-expressing cell line. This research was supported in part by NIH and US-Israel BARD grants to P.A.S.B. and the German Science Foundation (W.M.). Author Contributions: V.G.-C. and P.A.S.B. discovered the phenomenon of sweet ‘water-taste’ with Na-saccharin and other sweetness inhibitors, conceived and designed the perceptual experiments and collected the behavioural data. M.W. conducted the molecular, histological and imaging experiments. B.B. participated in the functional studies and coordination of the molecular experiments. All authors contributed to the design of parallel in vivo/ex vivo control experiments and to writing and editing the manuscript.
Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
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Galindo-Cuspinera, V., Winnig, M., Bufe, B. et al. A TAS1R receptor-based explanation of sweet ‘water-taste’. Nature 441, 354–357 (2006). https://doi.org/10.1038/nature04765
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