T2Rs function as bitter taste receptors

Bitter taste perception provides animals with critical protection against i ngestion of poisonous compounds. In the accompanying paper, we report the c haracterization of a large family of putative mammalian taste receptors (T2 Rs). Here we use a heterologous expression system to show that specific T2R s function as bitter taste receptors. A mouse T2R (mT2R-5) responds to the bitter tastant cycloheximide, and a human and a mouse receptor (hT2R-4 and mT2R-8) responded to denatonium and 6-n-propyl-2-thiouracil. Mice strains d eficient in their ability to detect cycloheximide have amino acid substitut ions in the mT2R-5 gene; these changes render the receptor significantly le ss responsive to cycloheximide. We also expressed mT2R-5 in insect cells an d demonstrate specific tastant-dependent activation of gustducin, a G prote in implicated in bitter signaling. Since a single taste receptor cell expre sses a large repertoire of T2Rs, these findings provide a plausible explana tion for the uniform bitter taste that is evoked by many structurally unrel ated toxic compounds.