Figure 1. Taste cells in taste buds. (a) Schematic diagram of different cell types. (b) Stem cell renewal, Source: 34. Reproduced with permission of Development.

Taste receptors act as intermediates and interact with taste stimuli or ligands to activate afferent nerves and transmit taste signals to the brain. The taste receptor genes are expressed either in all types of taste buds or specific taste buds. In FF and FL papillae, T1R1 and T1R3 form dimers to sense umami. In CV, FL, and FF papillae, T1R2 and T1R3 are coexpressed to transfer sweetness[41-46]. Meanwhile, the main site of expression of the T2R genes is circumvallate taste buds sensing bitterness[47,48]. Salty and sour tastes are mediated by channel-type receptors[49,50]. And various candidate sour taste receptors have been discovered, such as ACCN1[51], HCN1, HCN4[52], TASK-1[53]. They can work alone or in combination with other receptors. Terms of the two best-studied families of taste receptors, T1R and T2R, have seven transmembrane characteristics and sometimes dimers are formed between them to play the role of transmitting taste signals (Figure 2).

Besides, taste receptors are also expressed in other tissues. In addition to being widely expressed in taste buds to sense bitterness, T2Rs may also be found in the intestine and human airway smooth muscle (ASM)[10] to detect toxic substances[54]. Meanwhile, in cystic fibrosis bronchial epithelial (CuFi-1), normal bronchial epithelial (NuLi-1), airway smooth muscle (ASM), pulmonary artery smooth muscle (PASM), mammary epithelial, brain cells[55], and breast cancer cells, TAS2Rs had specific expression pattern[56]. For example, TAS2R3, 4, 5, 10, 13, 19, and 50 transcripts expressed at moderate levels and TAS2R14 and TAS2R20 (or TASR49) at high levels in the various tissues analyzed. Moreover, taste receptors also perform many other functions. It’s been reported that the T2R bitter receptor mediated the release of IL-25 from intestinal villi induced by Trichinella spiralis. This provides new ideas for the design of drugs against parasites[57]. This result preliminarily proves the role of bitter taste receptors in an immune response. Another evidence showed that quinine stimulated the airway’s innate immune defense by increasing the frequency of cilia beating and stimulating the production of NO in a manner consistent with T2R activation, thereby effectively alleviating chronic sinusitis[58]. Besides, T2R10 is expressed in pancreatic cancer tissues and various other cancer cell lines and regulated the chemotherapy resistance of tumor cells[59]. To study the function of receptors, it is inevitable to add exogenous ligands. TAS2R14 is the most widely regulated bitter taste receptor and is expressed in a variety of extraoral tissues. Therefore, more potent ligands are needed to study its function. The existing literature has designed a TAS2R14 agonist based on structure-based molecular modeling and experimental data. Furthermore, its effectiveness has been greatly improved[60]. For the most clearly studied bitter taste receptor, bitterDB contains more than 1,000 bitter taste molecules, while the related receptors are close to 800[61]. More recently, based on this database, researchers have developed the main calculation method for predicting bitterness based on the chemical structure of the compound, which has greatly promoted the development of the pharmaceutical industry[62]. In summary, taste receptors not only transmit taste in taste buds, but are also expressed in the intestine, airway and brain, and perform important functions such as immune defense.