The Molecular Receptive Ranges of Human TAS2R Bitter Taste Receptors

Abstract

Humans perceive thousands of compounds as bitter. In sharp contrast, only approximately 25 taste 2 receptors (TAS2R) bitter taste receptors have been identified, raising the question as to how the vast array of bitter compounds can be detected by such a limited number of sensors. To address this issue, we have challenged 25 human taste 2 receptors (hTAS2Rs) with 104 natural or synthetic bitter chemicals in a heterologous expression system. Thirteen cognate bitter compounds for 5 orphan receptors and 64 new compounds for previously identified receptors were discovered. Whereas some receptors recognized only few agonists, others displayed moderate or extreme tuning broadness. Thus, 3 hTAS2Rs together were able to detect approximately 50% of the substances used. Conversely, though 63 bitter substances activated only 1-3 receptors, 19 compounds stimulated up to 15 hTAS2Rs. Our data suggest that the detection of the numerous bitter chemicals is related to the molecular receptive ranges of hTAS2Rs.

Genetics of Taste and Smell

“…But whether there is greater or lesser individual variation in the perception of lethal bitter chemicals has gone unanswered—ethical concerns obviously prevent testing with these poisons in people. Cell-based assays with one or two human bitter receptors can be used to test the response to a wide range of poisons, 39 but this method provides only a partial answer to the question because artificial systems may not recreate the human taste experience.…”

“…Although PTC was first created in a chemistry laboratory and is probably not found in plants, there are many chemical relatives of PTC that stimulate the TAS2R38 bitter taste receptor. 39,46,47 At least one of these compounds is found in plant food (turnips), 48 and less similar but still related compounds are found in other plant species. 49 People with taster and nontaster alleles of TAS2R38 differ in their perception of vegetables (like watercress) that contain these PTC-like compounds.…”

“…64 ) Current studies suggest that PTC is unusual because only one of the 25 known bitter receptors is strongly stimulated by it, so the loss of this one receptor (TAS2R38) is consequential. 39 Other bitter molecules stimulate multiple receptors, and the loss of one may decrease but not eliminate the ability to detect that particular bitter molecule. 30,39,47,65-73 The perception of PTC is probably an extreme case of individual variation in bitter perception.…”

The Utility of the Artificial Taste Sensor in Evaluating the Bitterness of Drugs: Correlation with Responses of Human TASTE2 Receptors (hTAS2Rs)

“…3,4,6) Meyerhof et al have systematically investigated the molecular receptive ranges of bitter taste receptors using natural or synthetic bitter chemicals to challenge all 25 human TAS2Rs in transfected cells. 3) Correlation between Taste Sensor and hTAS2Rs…”

“…1) The detection of bitterness is mediated by the TASTE2 Receptor (TAS2R) family of G protein-coupled receptors, and humans have been found to have 25 of these (hTAS2Rs). [2][3][4][5] Information on the association of many bitter ligands with particular TAS2Rs, established by in vitro assay, can be accessed via the Bitter DB database 6) (http://bitterdb. agri.huji.ac.il/dbbitter.php).…”