Artificial sweeteners and salts producing a metallic taste sensation activate TRPV1 receptors

Abstract

Riera CE, Vogel H, Simon SA, le Coutre J. Artificial sweeteners and salts producing a metallic taste sensation activate TRPV1 receptors. Am J Physiol Regul Integr Comp Physiol 293: R626-R634, 2007. First published June 13, 2007; doi:10.1152/ajpregu.00286.2007.-Throughout the world many people use artificial sweeteners (AS) for the purpose of reducing caloric intake. The most prominently used of these molecules include saccharin, aspartame (Nutrasweet), acesulfame-K, and cyclamate. Despite the caloric advantage they provide, one key concern in their use is their aversive aftertaste that has been characterized on a sensory level as bitter and/or metallic. Recently, it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. To more fully understand the biology behind these phenomena we have addressed the question of whether AS could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the AS aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca 2ϩ imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons, we find that in both systems, AS activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. We also found that TRPV1 receptors are activated by CuSO 4, ZnSO4, and FeSO4, three salts known to produce a metallic taste sensation. In summary, our results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts. multisensory taste; pain; calcium imaging IN MANY FOODS, ARTIFICIAL sweeteners (AS) represent a major dietary supplement. Their consumption is involved with weight management, prevention of dental decay, and for diabetics the control of blood glucose. Saccharin, aspartame, and acesulfame-K are among the most commonly used AS. Cyclamate, although currently not approved for use in the United States, is used in more than 50 countries worldwide. Unlike sucrose, these compounds are not perceived to be sweet at all concentrations. In fact, for all these compounds, as concentration increases, the taste perception shifts from pleasant (sweet) toward unpleasant (bitter/metallic) (10,12,41). This shift has been explained by the activation at low concentrations of sweet tastant-sensing G protein-coupled receptors (GPCRs) T1R2/ T1R3 (23) and at higher concentrations, the activation of the bitter tastant sensing GPCRs, T2R43, and T2R44 for saccharin and acesulfame-K (21). Other taste sensations related to the aftertaste elicited by artificial sweeteners have been attributed ...

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“…As indicated by increases in fluorescence, after stimulation by CTDS, hTRPV1-expressing cells evoked large changes in voltage. Depolarizations were also observed in calcium-free HBSS, consistent with results showing that HEK293 cells expressing TRPV1 can be depolarized by the influx of cations through the TRPV1 channel (Ahern et al, 2005;Riera et al, 2007).…”

“…Previously, we showed that heterologously expressed hTRPV1 in HEK293 cells could be activated by FeSO 4 , ZnSO 4 , CuSO 4 , and MgSO 4 (Riera et al, 2007). To determine whether CTDS could also activate TRPM5 channels, we expressed hTRPM5 in HEK293 cells, and we measured evoked changes in voltage in response to CTDS.…”

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