Taste receptor
A taste receptor is a type of cellular receptor that facilitates the sensation of taste. When food or other substances enter the mouth, molecules interact with saliva and are bound to taste receptors in the oral cavity and other locations. Molecules which give a sensation of taste are considered "sapid".
Vertebrate taste receptors are divided into two families:
- Type 1, sweet, first characterized in 2001: –
- Type 2, bitter, first characterized in 2000: In humans there are 25 known different bitter receptors, in cats there are 12, in chickens there are three, and in mice there are 35 known different bitter receptors.
Tissue distribution
The gustatory system consists of taste receptor cells in taste buds. Taste buds, in turn, are contained in structures called papillae. There are three types of papillae involved in taste: fungiform papillae, foliate papillae, and circumvallate papillae.. Beyond the papillae, taste receptors are also in the palate and early parts of the digestive system like the larynx and upper esophagus. There are three cranial nerves that innervate the tongue; the vagus nerve, glossopharyngeal nerve, and the facial nerve. The glossopharyngeal nerve and the chorda tympani branch of the facial nerve innervate the TAS1R and TAS2R taste receptors. Next to the taste receptors in on the tongue, the gut epithelium is also equipped with a subtle chemosensory system that communicates the sensory information to several effector systems involved in the regulation of appetite, immune responses, and gastrointestinal motility.In 2010, researchers found bitter receptors in lung tissue, which cause airways to relax when a bitter substance is encountered. They believe this mechanism is evolutionarily adaptive because it helps clear lung infections, but could also be exploited to treat asthma and chronic obstructive pulmonary disease.
The sweet taste receptor can be found in various extra-oral organs throughout the human body such as the brain, heart, kidney, bladder, nasal respiratory epithelium and more. In most of the organs, the receptor function is unclear. The sweet taste receptor found in the gut and in the pancreas was found to play an important role in the metabolic regulation of the gut carbohydrate-sensing process and in insulin secretion. This receptor is also found in the bladder, suggesting that consumption of artificial sweeteners which activates this receptor might cause excessive bladder contraction.
Function
helps to identify toxins, maintain nutrition, and regulate appetite, immune responses, and gastrointestinal motility. Five basic tastes are recognized today: salty, sweet, bitter, sour, and umami. Salty and sour taste sensations are both detected through ion channels. Sweet, bitter, and umami tastes, however, are detected by way of G protein-coupled taste receptors.In addition, some agents can function as taste modifiers, as miraculin or curculin for sweet or sterubin to mask bitter.
Mechanism of action
The standard bitter, sweet, or umami taste receptor is a G protein-coupled receptor with seven transmembrane domains. Ligand binding at the taste receptors activate second messenger cascades to depolarize the taste cell. Gustducin is the most common taste Gα subunit, having a major role in TAS2R bitter taste reception. Gustducin is a homologue for transducin, a G-protein involved in vision transduction. Additionally, taste receptors share the use of the TRPM5 ion channel, as well as a phospholipase PLCβ2.Savory or glutamates (Umami)
The TAS1R1+TAS1R3 heterodimer receptor functions as an umami receptor, responding to L-amino acid binding, especially L-glutamate. The umami taste is most frequently associated with the food additive monosodium glutamate and can be enhanced through the binding of inosine monophosphate and guanosine monophosphate molecules. TAS1R1+3 expressing cells are found mostly in the fungiform papillae at the tip and edges of the tongue and palate taste receptor cells in the roof of the mouth. These cells are shown to synapse upon the chorda tympani nerves to send their signals to the brain, although some activation of the glossopharyngeal nerve has been found.Alternative candidate umami taste receptors include splice variants of metabotropic glutamate receptors, mGluR4 and mGluR1, and the NMDA receptor.
During the evolution of songbirds, the umami taste receptor has undergone structural modifications in the ligand binding site, enabling these birds to sense the sweet taste by this receptor.
Sweet
The TAS1R2+TAS1R3 heterodimer receptor functions as the sweet receptor by binding to a wide variety of sugars and sugar substitutes. TAS1R2+3 expressing cells are found in circumvallate papillae and foliate papillae near the back of the tongue and palate taste receptor cells in the roof of the mouth. These cells are shown to synapse upon the chorda tympani and glossopharyngeal nerves to send their signals to the brain.Sensing of the sweet taste has changed throughout the evolution of different animals. Mammals sense the sweet taste by transferring the signal through the heterodimer T1R2/T1R3, the sweet taste receptor. In birds, however, the T1R2 monomer does not exist and they sense the sweet taste through the heterodimer T1R1/T1R3, the umami taste receptor, which has gone through modifications during their evolution. A recently conducted study showed that along the evolution stages of songbirds, there was a decrease in the ability to sense the umami taste, and an increase in the ability to sense the sweet taste, whereas the primordial songbird parent could only sense the umami taste. Researchers found a possible explanation for this phenomenon to be a structural change in the ligand binding site of the umami receptor between the sweet taste sensing and non-sensing songbirds. It is assumed that a mutation in the binding site occurred over time, which allowed them to sense the sweet taste through the umami taste receptor.
Bitter
The TAS2R proteins function as bitter taste receptors. There are 43 human TAS2R genes, each of which lacks introns and codes for a GPCR protein. These proteins, as opposed to TAS1R proteins, have short extracellular domains and are located in circumvallate papillae, palate, foliate papillae, and epiglottis taste buds, with reduced expression in fungiform papillae. Though it is certain that multiple TAS2Rs are expressed in one taste receptor cell, it is still debated whether mammals can distinguish between the tastes of different bitter ligands. Some overlap must occur, however, as there are far more bitter compounds than there are TAS2R genes. In silico modelling results suggest that bitterness receptors tend to cluster into three distinct groups based on their interaction with bitter ligands relevant to wine. Common bitter ligands include cycloheximide, denatonium, PROP, PTC, and β-glucopyranosides.Signal transduction of bitter stimuli is accomplished via the α-subunit of gustducin. This G protein subunit activates a taste phosphodiesterase and decreases cyclic nucleotide levels. Further steps in the transduction pathway are still unknown. The βγ-subunit of gustducin also mediates taste by activating IP3 and DAG. These second messengers may open gated ion channels or may cause release of internal calcium. Though all TAS2Rs are located in gustducin-containing cells, knockout of gustducin does not completely abolish sensitivity to bitter compounds, suggesting a redundant mechanism for bitter tasting. One proposed mechanism for gustducin-independent bitter tasting is via ion channel interaction by specific bitter ligands, similar to the ion channel interaction which occurs in the tasting of sour and salty stimuli.
One of the best-researched TAS2R proteins is TAS2R38, which contributes to the tasting of both PROP and PTC. It is the first taste receptor whose polymorphisms are shown to be responsible for differences in taste perception. Current studies are focused on determining other such taste phenotype-determining polymorphisms. More recent studies show that genetic polymorphisms in other bitter taste receptor genes influence bitter taste perception of caffeine, quinine and denatonium benzoate.
It has been demonstrated that bitterness receptors play an important role in an innate immune system of airway ciliated epithelium tissues.
This innate immune system adds an "active fortress" to the physical Immune system surface barrier.
This fixed immune system is activated by the binding of ligands to specific receptors.
These natural ligands are bacterial markers, for TAS2R38 example: acyl-homoserine lactones or quinolones produced by Pseudomonas aeruginosa. To defend against predators, some plants have produced mimic bacterial markers substances. These plant mimes are interpreted by the tongue, and the brain, as being bitterness.
The fixed immune system receptors are identical to the bitter taste receptors, TAS2R. Bitterness substances are agonist of TAS2R fixed immune system.
The innate immune system uses nitric oxide and defensins which are capable of destroying bacteria, and also viruses.
These fixed innate immune systems are known in other epithelial tissues than upper airway, for example: breast, gut and also human skin
Bitter molecules, their associated bitter taste receptors, and the sequences and homology models of bitter taste receptors, are available via BitterDB.