Bitter-sweet taste: the taste receptors

Since we were children, we were taught at school that taste is one of our most important sense. Indeed, since we are born, this represents a way to be exposed to the world and learn to discriminate several tastes, which helps us to recognize also specific types of food or feelings when eating them. Of course, human nature evolved progressively to develop sensitive taste skills, at the beginning as a matter of survival. Although now our needs are different, these important genetic feature survived, and we are still capable of distinguish among several types of taste. In this article, an explanation of what determines the sensitivity to specific tastes is going to be provided, with some molecular and evolutionary explanations on how the taste sense evolved in animals.

Taste skills: why were they important in the past?

Many vertebrates can detect the same five basic tastes as humans can taste (with some differences). The sense of taste has classically been limited to the 5 basic taste qualities: sweet, salty, sour, bitter, and umami or savoury. Taste is crucial in species evolution for survival and reproduction, as it had the role of guiding animals to seek more nutritious, energy-rich foods, while avoiding toxic substances. This would have ensured energy acquisition, prevented dangerous poisoning, and prepared the body to digest food, with specific evolutionary adaptations which were linked to ecosystems' changes and dietary modifications.

How complex is the regulation of the taste in animals?

As it may be understood from the previous paragraphs, taste is regulated by several genes, which allow an extensive versatility in tasting several types of foods, and which are finely regulated genetically. As a matter of fact, in many animal species, taste also evolved as a loss of function mutation (so, animals lost their ability to distinguish specific tastes), and this is still a topic under study, as it has not been clarified yet if the loss of function depended on changes in animals' habits and diet, or if, viceversa, the loss of function mutation led animals to change their food preferences.

Which genes are involved in the regulation of taste?

Several genes have been identified as essential in regulating the taste sense. Many of them are important for the expression of taste receptors, G protein-coupled receptors (GPCRs) and ion channels, proteins involved in the regulation of taste functioning on a molecular level. Taste receptors (TASRs) in the oral cavity bind molecules contained in food and make us understand the differences among tastes depending on the type of food we are having. These allow animals to recognize mostly umami, sweet and bitter taste (although other receptors, like glutamate receptors and NMDA ion channels also help in recognizing the umami taste.

Other important ion channels for taste are HCN and ENaC, important, respectively, to detect sour and salt tastes. Carbonic anhydrase 4, or CA-IV, is an enzyme which instead regulates the recognition of carbonated water. Finally, also some non-taste receptors belonging to the G protein-coupled receptors (GPCRs) family are involved in taste functioning. Examples of this are GPR120 and GPR40, which are also called free fatty acids receptors, because they allow the perception of fat taste. Also CD36 receptor is considered able to bind long chain fatty acids, regulating possibly the perception of fat.

Molecular mechanisms of taste receptors activation

TASRs are G protein-coupled receptors that, upon activation mediated by tasteful compounds, activate signalling cascades that depend on the specificity of the stimuli that these receptors are binding. Although these receptors are important, also ion channels are essential for the taste transduction, and this is why these are located both in the apical and basolateral membranes of taste cells. These include voltage-gated sodium, potassium and calcium channels, that produce depolarizing potentials when taste cells interact with chemical stimuli. The resulting receptor potentials raise intracellular calcium sufficiently to fuse synaptic vesicles and allow the synaptic transmission, thus eliciting action potentials in the afferent axons. In general, the greater the tastant concentration, the greater the depolarization of the taste cell, with the type of the tastant determining the type of response generated.

For example sweeteners such as the saccharides cause the activation of GPCRs, which depolarize taste cells by activating adenylate cyclase, which in turn increases the cAMP concentration that will either directly or indirectly close basolateral potassium channels. Synthetic sweeteners, such as saccharine, activate different GPCRs that in turn activate the enzyme phospholipase C, to produce two substrates called IP3 and DAG. An increase in IP3 raises intracellular calcium concentration, leading to transmitter release. An increase in DAG activates the kinase PKA, and PKA in turn phosphorylates and closes basolateral potassium channels, further contributing to this effect.

Bitter- tasting organic compounds typically bind to GPCRs that activate gustducin, which in turn activates phosphodiesterase, thus lowering the cyclic nucleotide concentration and closing cyclic nucleotide-gated channels on the basolateral membranes of taste cells.

Why does the same food taste differently for two different people?

We all have bumps on our tongue called papillae, which present taste buds that react to the different flavours in food when they reach our mouth. However, not only the amount of papillae on our tongue varies from person to person, but also the expression of the taste receptors and ion channels can be variable, due to genetic polymorphisms and variations in expression levels of genes involved in taste receptors. This can cause differences in the way we taste the same food!

Take-home message

As described in this article, there are several reasons (genetic, physiological, chemical, environmental) why we perceive differently the taste of several food. Although we already found out interesting findings on how the taste sense physiologically works, especially for the molecular mechanisms regulating this process, we still need more research and study to understand fully how this system works to take advantage of this knowledge for an optimal therapeutic strategy.

References

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