Bitter taste receptor family (TAS2R) (TAS2R)

The Bitter taste receptor family (TAS2R) consists of approximately 25 functional G protein-coupled receptors in humans that were originally identified for their role in detecting bitter-tasting substances on the tongue [1]. Beyond the oral cavity, TAS2Rs are expressed in various tissues including the respiratory tract, gastrointestinal system, and immune cells, where they serve as sentinel receptors [2]. In the lungs, activation of TAS2Rs on airway smooth muscle cells by pan-TAS2R agonists induces potent bronchodilation, making them a promising target for treating obstructive airway diseases like asthma and COPD [3]. In the gut, they influence the release of metabolic hormones, while in the upper airways, they trigger innate immune responses against bacterial pathogens [4]. Because many bitter compounds activate multiple TAS2R subtypes, the term pan-TAS2R refers to the collective targeting of these receptors to achieve a broad therapeutic effect [5]. These receptors are characterized by their ability to recognize a diverse array of chemical structures, ranging from small ions to complex plant alkaloids [1]. Therapeutic development focuses on leveraging their bronchodilatory and anti-inflammatory properties while managing the challenges of systemic exposure and bitter taste perception [2, 3].

Other names

T2RBitter taste receptorsTaste receptor family BTaste receptor type 2TAS2Rs

Agonism of TAS2R receptors triggers a G protein-mediated signaling cascade, typically involving the G protein gustducin, which activates phospholipase C beta-2 (PLCβ2) and leads to the release of intracellular calcium [1, 3]. In airway smooth muscle, this calcium release paradoxically leads to the activation of large-conductance calcium-activated potassium (BKCa) channels, resulting in membrane hyperpolarization and muscle relaxation [3, 5]. In other tissues, such as the gut or immune cells, the same signaling pathway modulates hormone secretion or the release of antimicrobial peptides [2, 4].