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.