TAS2R38

Taste receptor 2 member 38 is a

As with all TAS2R proteins, TAS2R38 utilizes the G-protein gustducin as its primary method of signal transduction. Both the α- and βγ-subunits are crucial to the transmission of the taste signal.^[9] See: taste receptor.

Ligands

To date, a total of 23 distinct ligands have been identified for the T2R38 bitter taste receptor. These ligands have been extensively cataloged and documented in the comprehensive database known as BitterDB. Within this repository of bitter taste information, notable ligands such as PTC (phenylthiocarbamide) and PROP ( 6-n-propylthiouracil) have been extensively studied and are widely recognized. Additionally, T2R38 has been found to interact with other intriguing ligands, including limonin, a compound commonly found in citrus fruits, cyclamate, an artificial sweetener, and Chlorpheniramine, an antihistamine employed for the management of allergic conditions. The range of ligands recognized by the T2R38 receptor adds to our understanding of the complex molecular interactions involved in the perception of bitter taste.

Tissue distribution

Taste GPCRs are expressed not only in the oral cavity but also in extra-oral tissues. Bitter taste receptors that are expressed in extra-oral tissues fill a variety of functional physiological roles.^[10] TAS2R38 is expressed in many tissues, such as human sinonasal epithelial cells, airway smooth muscle, monocytes, macrophages, heart, arteries, thyroid, skin, etc.^[11]

Clinical significance

PTC sensitivity

Differential ability to taste the bitter compound phenylthiocarbamide (PTC) was discovered more than 80 years ago.

Because bitter substances are usually toxic, the presence of a “nontaster” geno- and phenotype seems evolutionarily undesirable. Several studies have suggested, however, that the AVI polymorphism may code for an entirely new receptor which processes a different and as-yet undiscovered bitter compound.^[7][12] Furthermore, the presence of the nontaster allele may reflect the desirability of maintaining a mostly heterozygous population; this group of people may possess flexibility in their bitter taste perception, enabling them to avoid a greater number of toxins than either homozygotic group.^[12] Other studies, however, suggest that the AVI nontaster genotype has no functional ligand.^[16] For an evolutionary perspective, the reference sequences for gorillas and chimps have the PAV haplotype, while mouse and rat have PAI.^[17]

This genotypical alteration of taste phenotype is currently unique to TAS2R38. Though genotype has been proposed as a mechanism for determining individual taste preferences, TAS2R38 is so far the first and only taste receptor to display this property.^[8]

PROP sensitivity

The TAS2R38 protein also confers sensitivity to the bitter compound 6-n-propylthiouracil (PROP). Because perception of PROP bitterness has been associated with supertasting, and because TAS2R38 genotypes associate with PROP-tasting phenotypes, it has been proposed that TAS2R38 genotypes may have a role in supertasting capabilities. It appears that while TAS2R38 genotypes determine a threshold of PROP tasting abilities, the genotypes cannot account for the differences in tasting amongst each threshold group. For example, some PAV/PAV homozygotes perceive PROP to be more bitter than others, and TAS2R38 genotype cannot account for these differences. Furthermore, some heterozygotes may become PROP supertasters (despite a lack of two PAV alleles), indicating overlap between PROP bitterness levels and varying TAS2R38 genotypes. These results illustrate that a mechanism beyond TAS2R38 genotype contributes to supertasting capabilities.^[16]

Because

As with watercress, mustard greens, turnip, broccoli and horseradish, human perception of bitterness in rutabaga is governed by a gene affecting the TAS2R bitter receptor, which detects the glucosinolates in rutabaga. Sensitive individuals with the genotype PAV/PAV (supertasters) find rutabaga twice as bitter as insensitive subjects (AVI/AVI). The difference for the mixed type (PAV/AVI) is insignificant for rutabaga.^[20] As a result, sensitive individuals may find some rutabagas too bitter to eat.

Drug consumption

PROP bitterness and TAS2R38 genotype have been further examined in relation to alcohol intake. Research has suggested that the level of alcohol consumption may correlate with the level of perceived bitterness of ethanol; those people who find PROP to be more bitter also find the taste of ethanol to be less pleasant. Again, however, correlates between TAS2R38 genotype and the taste of alcohol were not significant: the TAS2R38 genotype could not predict the intensity of alcohol bitterness (though PROP bitterness did correlate with alcohol bitterness). Genotype could predict alcohol intake; those with nontaster alleles were more likely to consume more alcohol over the course of the year. Again, a second genetic factor seems to contribute to these phenomena. A gene altering the density of fungiform papillae may provide this second factor.^[5]

PTC sensitivity and TAS2R38 genotype have been researched in relation to smoking behavior. It was suggested in a research that non-tasters may be likely to smoke cigarettes more, compared to PTC tasters, that is due to the fact that tobacco smoke contains chemical substances that activate TAS2R38.^[21]

Gene variation in TAS2R38 was associated with food intake and preference, and obesity risk. The genetic variation is involved with consumption of fruits, sweets and fat, it was shown in a research that non-tasters had higher intake of these food products that might lead to obesity.^[22]

Pathogen resistance

Bitter taste receptors exhibit expression in various cell types within the sinonasal and airway regions. Other ligands that activate T2R38 are N-Acyl homoserine lactones (AHLs) are a class of signaling molecules involved in bacterial quorum sensing. Upon encountering these agonists, the receptors initiate a signaling cascade that relies on T2R activation. Consequently, this cascade triggers the release of nitric oxide (NO), a potent bactericidal agent, thereby promoting both bactericidal activity and an enhancement in mucociliary clearance (MCC).^[23]

Notably, a correlation has been observed between medically refractory chronic rhinosinusitis (CRS) and nonprotective genetic variants of the TAS2R38 gene. Certain polymorphisms associated with TAS2R38 have been linked to decreased incidence of allergies, asthma, nasal polyposis, aspirin sensitivity, and diabetes among CRS patients, although statistical significance has not yet been established.^[24]

Moreover, the TAS2R38 genotype has been identified as an independent risk factor for patients who experience treatment failure with medical interventions, subsequently necessitating surgical intervention.

See also

• Supertaster
• Taste receptor
• PTC tasting

References