Human bitter taste perception.

Bitter taste perception is innate and induces aversive reactions. Since numerous harmful compounds, including secondary plant metabolites, synthetic chemicals, inorganic ions and rancid fats, do taste bitter, this basic taste modality may be considered as a defence mechanism against the ingestion of potential poisons. For a complete understanding of this defence mechanism it is obligatory to identify and characterize the chemical detectors of the bitter compounds, which display the remarkable ability to recognize thousands of different chemicals. Screening of the genome data bases ultimately led to the discovery of a novel gene family of ∼40 members in mice and ∼30 in humans. Some of the genes identified by this approach are located within chromosomal loci associated with tasting various distinct bitter compounds (Adler et al., 2000; Matsunami et al., 2000; Bufe et al., 2002). Therefore, these genes encoding G-proteincoupled receptors, TAS2Rs (previously referred to as T2Rs or TRBs), have been suggested to represent bitter taste receptors. Several lines of independent evidence further support this assumption (Adler et al., 2000; Chandrashekar et al., 2000; Matsunami et al., 2000). First, the expression pattern of these genes on the rodent tongue was consistent with that of bitter taste receptors. Secondly, functional expression studies identified the bitter compound cycloheximide as an agonist for mTAS2R105. Thirdly, mice strains with impaired cycloheximide tasting have variant mTAS2R105 genes encoding receptors that are less responsive to cycloheximide. Fourthly, mTAS2R105 couples in vitro to α-gustducin (Chandrashekar et al., 2000), a G-protein α-subunit expressed in taste tissue that has amply been shown before to play a role in bitter taste transduction (Margolskee, 2002). Although this question has not been directly addressed, these investigations led to the impression of a narrow tuning of bitter taste receptors and raised the intriguing problem of how organisms that are equipped with a limited number of TAS2R genes are able to perceive numerous chemicals bitter. In the present report we address two questions that are important for the understanding of bitter taste in general and human bitter taste in particular. First, given the largely uncharacterized receptor repertoire, are all TAS2Rs true bitter taste receptors and, secondly, can their broad tuning explain how humans equipped with a fairly small number of TAS2R genes are able to perceive thousands of bitter compounds.