T2Rs

Type 2 taste receptors (T2Rs) are a family of G protein-coupled receptors responsible for bitter taste perception. They are expressed mainly in the type 2 taste receptor cells within taste buds on the tongue and other oral tissues and are encoded by the TAS2R gene family. In humans, about 25 TAS2R genes are functional, with many additional pseudogenes; the repertoire varies across species and individuals, contributing to differences in bitterness sensitivity. A well-studied example is TAS2R38, whose common PAV and AVI haplotypes determine the perceived intensity of the bitter compound PROP (PTC).

Signaling begins when a bitter compound binds a T2R, activating G proteins such as gustducin and triggering a phospholipase Cβ2–IP3–Ca2+ signaling cascade. The rise in intracellular calcium activates the TRPM5 cation channel, leading to cell depolarization and the release of signaling molecules, notably ATP, through CALHM1/3 channels to activate gustatory neurons.

The bitter receptor set is diverse and displays broad, overlapping ligand specificity; individual receptors can be activated by multiple bitter substances and certain bitter compounds can activate several receptors. In addition to the tongue, T2Rs are expressed in extraoral tissues including the respiratory epithelium, gastrointestinal tract, and certain brain regions, where they are implicated in innate immune responses, airway regulation, and hormonal signaling. These roles are the subject of ongoing research.

Evolutionarily, bitter taste helps detect potentially toxic compounds, contributing to dietary choices and protection against ingestion of harmful substances. The TAS2R gene family shows rapid evolution and diversification across species, reflecting ecological dietary pressures. T2Rs remain an active area of study in sensory biology, nutrition, and pharmacology.