Bitter Taste Receptors for Saccharin and Acesulfame K

Abstract

Weight-conscious subjects and diabetics use the sulfonyl amide sweeteners saccharin and acesulfame K to reduce their calorie and sugar intake. However, the intrinsic bitter aftertaste, which is caused by unknown mechanisms, limits the use of these sweeteners. Here, we show by functional expression experiments in human embryonic kidney cells that saccharin and acesulfame K activate two members of the human TAS2R family (hTAS2R43 and hTAS2R44) at concentrations known to stimulate bitter taste. These receptors are expressed in tongue taste papillae. Moreover, the sweet inhibitor lactisole did not block the responses of cells transfected with TAS2R43 and TAS2R44, whereas it did block the response of cells expressing the sweet taste receptor heteromer hTAS1R2-hTAS1R3. The two receptors were also activated by nanomolar concentrations of aristolochic acid, a purely bitter-tasting compound. Thus, hTAS2R43 and hTAS2R44 function as cognate bitter taste receptors and do not contribute to the sweet taste of saccharin and acesulfame K. Consistent with the in vitro data, cross-adaptation studies in human subjects also support the existence of common receptors for both sulfonyl amide sweeteners.

Time Course of Elevated Ethanol Intake in Adolescent Relative to Adult Rats Under Continuous, Voluntary‐Access Conditions

“…Animals consumed more of an ethanol solution if it was sweetened (and calorically supplemented) with sucrose, but similar amounts when the solution was unsweetened or saccharin-sweetened. Saccharin, while mainly possessing sweet taste quality, has also been shown by in vitro data to have an intrinsically bitter aftertaste, presumably due to the activation of not only sweet taste receptors but also receptors sensitive to bitter components within human tongue taste papillae (Kuhn et al, 2004). There is some evidence that saccharin may have an aversive taste component in rats as well (Dess, 1993).…”

Artificial Sweeteners Stimulate Adipogenesis and Suppress Lipolysis Independently of Sweet Taste Receptors

“…An additional possibility for how artificial sweeteners mediate effects in preadipocytes and adipocytes is through bitter taste receptors with which saccharin and AceK interact in the tongue to cause the aversive "metallic" aftertaste at low mM concentrations (61,62). To date, expression of one bitter taste receptor in an adipogenic system has been published, Tas2R46 in human mesenchymal stem cells (63).…”

Signal transduction and information processing in mammalian taste buds

“…The role of T2Rs in bitter taste was confirmed and extended by more recent studies in native tissues: mice, genetically engineered to express candidate human bitter receptors such as hTAS2R38 for taste stimuli to which rodents normally do not respond (in the case of hTAS2R38, phenylthiocarbamide, see Table 3), manifest a taste aversion to those compounds [78]. In addition, mice expressing a κ-opioid receptor under the control of a bitter receptor promoter Salicin (a bitter-tasting beta-glucopyranoside found in the bark of willows and related to aspirin, acetylsalicylic acid) hTAS2R38 [149] Phenylthiocarbamide (PTC), propylthiouracil (PROP) hTAS2R43, hTAS2R44 [150] High concentrations of saccharin and acesulfame K (artificial sweeteners that evoke a bitter aftertaste in humans) hTas2R46 [81] Absinthin, strychnine, and denatonium (the latter being one of the most intensely bitter compounds for humans and used, for example, as a deterrent for nail biting and thumb sucking) show a taste aversion to spiradoline, an opioid agonist that is normally tasteless to mice [78]. These studies validate the role of T2Rs (Tas2Rs) in bitter taste.…”