Differential modulation of the lactisole ‘Sweet Water Taste’ by sweeteners

Abstract

Pre-exposure to taste stimuli and certain chemicals can cause water to have a taste. Here we studied further the ‘sweet water taste’ (SWT) perceived after exposure to the sweet taste inhibitor lactisole. Experiment 1 investigated an incidental observation that presenting lactisole in mixture with sucrose reduced the intensity of the SWT. The results confirmed this observation and also showed that rinsing with sucrose after lactisole could completely eliminate the SWT. The generalizability of these findings was investigated in experiment 2 by presenting 5 additional sweeteners before, during, or after exposure to lactisole. The results found with sucrose were replicated with fructose and cyclamate, but the 3 other sweeteners were less effective suppressors of the SWT, and the 2 sweeteners having the highest potency initially enhanced it. A third experiment investigated these interactions on the tongue tip and found that the lactisole SWT was perceived only when water was actively flowed across the tongue. The same experiment yielded evidence against the possibility that suppression of the SWT following exposure to sweeteners is an aftereffect of receptor activation while providing additional support for a role of sweetener potency. Collectively these results provide new evidence that complex inhibitory and excitatory interactions occur between lactisole and agonists of the sweet taste receptor TAS1R2-TAS1R3. Receptor mechanisms that may be responsible for these interactions are discussed in the context of the current model of the SWT and the possible contribution of allosteric modulation.

A novel functional screening assay to monitor sweet taste receptor activation in vitro

“…We also observed that efficiency of inhibition was influenced by the time of incubation. As shown by Alvarado et al, 49 sucrose to activate a signaling response. Thus, depending on the effects studied, shorter or longer stimulation periods might be considered to obtain optimal results in inhibition or enhancing assays respectively.…”

Utilizing the Off-Target Effects of T1R3 Antagonist Lactisole to Enhance Nitric Oxide Production in Basal Airway Epithelial Cells

“…Both sweet and umami taste signaling pathways are thought to share a common component, the GPCR T1R3. In humans, lactisole inhibits the perceived taste of both sweet [ 12 ] and umami [ 13 ] compounds at concentrations of >1 mM. Lactisole binds to the transmembrane domains of T1R3 where it interrupts T1R3-mediated Ca 2+ signaling [ 11 , 27 , 28 ].…”

“…Lactisole has been shown to inhibit T1R3 through interactions with a binding pocket within T1R3′s transmembrane domain [ 11 ]. Once bound, lactisole inhibits the downstream Ca 2+ pathways activated by the detection of sweet [ 12 ] or umami molecules [ 13 ]. Consequently, in human taste signaling pathways, lactisole inhibits the detection of both sweet and savory molecules.…”

“…Consequently, in human taste signaling pathways, lactisole inhibits the detection of both sweet and savory molecules. In addition to biochemical and psychophysical research studies, lactisole is also used in the food industry in high-sugar-content foods such as fruit jams or jellies to reduce sweetness and allow other flavors to be perceived [ 10 , 11 , 12 , 13 ]. However, while the molecular interactions of lactisole with T1R3 have been examined in detail [ 11 ], to our knowledge, off-target effects of lactisole have not been investigated.…”

TAS1 receptors. An overview of their functions, expression and genetic variations

“…These mechanisms can be explained by the allosteric properties of the receptors and the different binding sites of the ligands at high and low concentrations. This supplementary binding induces loss of sweet perception (Alvarado et al, 2017;Galindo-Cuspinera et al, 2006). The activity of the TAS1R2/TAS1R3 agonist, miraculin, is dependent on both intracellular and extracellular pH with lower extracellular pH enhancing the sweetness sensation.…”