The Sweet Taste of Losing One's Inhibition

Abstract

Although sodium saccharin (Na-saccharin) is used as a sweetener, high concentrations taste mostly bitter--especially with consecutive exposures. Rinsing the bitter taste from your mouth leads to a sort of taste "after-image," so that the water tastes sweet, in what is referred to as a sweet "water-taste." Galindo-Cuspinera et al. found that, when mixed with sweet substances, various compounds that elicit sweet water-tastes, including lactisole, MgSO 4 , high concentrations of Na-saccharin, and acesulfame-K, inhibited sweetness. Sweeteners that do not elicit a sweet water-taste, such as Na-cyclamate, did not inhibit the sweetness of other sweet substances. Using calcium imaging to monitor the responses of human embryonic kidney cells transfected with the heteromeric human sweet taste receptor hTAS1R2-hTAS1R3, the authors found that responses to increasing concentrations of Na-saccharin or acesulfame-K peaked and declined in a manner that paralleled the loss of sweetness perceived by human tasters. Similarly, single-cell calcium imaging revealed that high concentrations of Na-saccharin inhibited the response to other sweeteners and that both Na-saccharin and acesulfame-K produced an off-response when rinsed from the cells (that is, the receptors were stimulated when the ligand was removed; this is analogous to the perceptual sweet water-taste). The authors interpret these data in terms of a two-state allosteric model for the sweetness receptor, with substances such as Na-saccharin or acesulfame-K binding to a high-affinity activating site at low concentrations and binding to a lower affinity site that shifts receptor equilibrium toward an inactive conformation at higher concentrations. In this model, rinsing leads to the preferential loss of these substances from the low-affinity inhibitory site and thus to a rebound perception of sweetness. V. Galindo-Cuspinera, M. Winnig, B. Bufe, W. Meyerhof, P. A. S. Breslin, A TAS1R receptor-based explanation of sweet "water-taste." Nature 441 , 354-357 (2006). [PubMed]