Besides the oral cavity, bitter taste receptors can also be found in non-gustatory tissues. In this study, functional experiments combined with molecular modeling were conducted to investigate the activation of human and mouse bitter taste receptors by bile acids. The results showed that several receptors were responsive to bile acids at concentrations found in human body fluids, suggesting a potential physiological role of non-gustatory bitter receptors as sensors for endogenous bile acid levels.
Beside the oral cavity, bitter taste receptors are expressed in several non-gustatory tissues. Whether extra-oral bitter taste receptors function as sensors for endogenous agonists is unknown. To address this question, we devised functional experiments combined with molecular modeling approaches to investigate human and mouse receptors using a variety of bile acids as candidate agonists. We show that five human and six mouse receptors are responsive to an array of bile acids. Moreover, their activation threshold concentrations match published data of bile acid concentrations in human body fluids, suggesting a putative physiological activation of non-gustatory bitter receptors. We conclude that these receptors could serve as sensors for endogenous bile acid levels. These results also indicate that bitter receptor evolution may not be driven solely by foodstuff or xenobiotic stimuli, but also depend on endogenous ligands. The determined bitter receptor activation profiles of bile acids now enable detailed physiological model studies. Using a combined experimental-computational approach, the activation profiles of human and mouse bitter taste receptors, TAS2Rs and Tas2rs, by bile acids is described, suggesting a physiological role of bile acids for taste receptors in non-gustatory tissues.
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