Constitutive activity of bitter taste receptors (T2Rs).

G protein-coupled receptors (GPCRs) play a vital role in transmitting an extracellular stimuli or signal into an intracellular response in various cells. In some scenarios, GPCRs or their mutants can also signal in the absence of an agonist or an external stimulus, referred to as basal or constitutive activity, and those mutants are termed constitutively active mutants (CAMs). Bitter taste is one of the five basic tastes and is mediated by bitter taste receptors (T2Rs), which belong to the GPCR superfamily. The 25 T2Rs present in humans do not belong to any of the major GPCR classes, and their classification is ambiguous. The characterization of T2Rs in many extraoral tissues including the airways and upper respiratory tract, where they were shown to cause bronchodilation and influence host susceptibility to infection, underscores the therapeutic relevance of these receptors. Recent structure-function and pharmacological studies on T2Rs led to the identification of CAMs. In this review, we summarize the major findings on constitutive activity of T2Rs and their diverse roles. We discuss the usefulness of the T2R CAMs in terms of the discovery of bitter taste blockers, elucidating the mechanisms of T2R activation and dissecting the physiological pathways.