Sweet Taste Signaling
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Sweet Taste Signaling
The sense of taste plays a critical role in the life and nutritional status of humans and other organisms. Human taste perception may be categorized according to four well known and widely accepted descriptors, sweet, bitter, salty, and sour (corresponding to particular taste qualities or modalities), and two more controversial qualities: fat and amino acid taste. In addition to these basic tastes, the taste buds also detect a meat-like taste known as umami in protein-rich food. The food chemicals that produce tastes set off different reactions from the taste buds with a main goal of sending signals along nerve fibers to the brain for interpretation. The perception of bitter taste is essential for its protective value, enabling humans to avoid potentially deadly plant alkaloids and other environmental toxins (Ref.1). On the tongue, the taste buds are mounted in special folds and protrusions called papillae. In humans, there are three types of sensory papillae. The fungiform papillae are located on the most anterior part of the tongue and generally contain one to several taste buds per papilla. The foliate papillae (15-30) are situated on the edge of the tongue slightly anterior of the circumvallate line. They are predominantly sensitive to sour tastes. The circumvallate papillae (7-15) are situated on the circumvallate line and confer sour/bitter sensitivity to the posterior two-thirds of the tongue. In total, an adult human may have several thousand taste buds.

The taste buds are specialized "onion-shaped" structures that are distributed throughout the oral cavity and comprise 50-100 individual TRCs (Taste Receptor Cells) whose apical and basal sides are separated by cation-selective tight junctions, so called because they are permeable only to small cations and anions. Because of their moderate cation selectivity, tight junctions can influence the taste of salts and acids. The restricted diffusion of anions provides a rational explanation of why NaCl tastes different from sodium gluconate and why citric acid tastes different from HCl. Taste sensation is realized in the mouth when the chemicals in food are dissolved by saliva. The free floating molecules are then able to enter a taste bud through the pore at its center. The taste bud is activated by different mechanisms depending on the type of taste, which then activates the appropriate cranial nerves. The sensations of bitter and sweet tastes are initiated by the interaction of sapid molecules, "tastants" with GPCR (G-Protein-Coupled Receptors) in the apical membranes of TRCs. The apical surface of TRCs, which makes contact with the oral cavity, is rich in convoluted microvilli containing GPCRs, ion channels, and other transduction elements (Ref.2 & 3). These proteins serve as receptors for sensory qualities such as salty, sour, sweet, umami and bitter taste, and trigger the downstream transduction events within taste cells. Included among these events is the firing of action potentials, which taste cells, like neurons, are able to generate by means of voltage-gated Na+, K+ and Ca2+ channels.

Sweet taste responds to soluble carbohydrates present in sufficient concentrations in the oral cavity, guiding high-calorie intake. It has a strong hedonic (pleasant) effect. The combination of T1R2 and T1R3 recognizes natural sugars, such as sucrose and glucose, and artificial or synthetic sweeteners, such as saccharin, acesulfame and D-Amino acids. Like bitter-responsive cells, sweet-responsive cells use both cyclic nucleotides (cAMP and cGMP) and IP3 (Inositol1, 4, 5-Trisphosphate) as second messengers. Although a variety of mechanisms have been proposed for taste transduction, all three modalities (sweet, salt and bitter) use elements of a common pathway; receptors signal through a heterotrimeric G-protein to PLC-Beta2 (Phospholipase-C-Beta2), which breaks down PIP2 (Phosphatidylinositol 4,5-Bisphosphate) into IP3 and DAG (Diacylglycerol). IP3 opens Ca2+-release channels to elevate intracellular Ca2+ (Ref.4) and activate Calm (Calmodulin). In the case of saccharides, activation of the GPCR activates ACs (Adenylate Cyclase), increasing cAMP (Cyclic Adenosine 3’, 5’-Monophosphate) that either directly or indirectly (via cAMP-dependent protein kinase) close basolateral KCn (K+ Channels), depolarizing TRCs. However, the balance between the activities of ACs and PDEs (Phosphodiesterases) determine the level of cAMP in cells. Synthetic sweeteners saccharine and D-Amino acids activate a different GPCR that in turn activates PLC to produce IP3 and DAG. The former increases intracellular Ca2+, and the latter phosphorylates and closes basolateral KCn (Ref.2).

Like other taste qualities, sweet taste is modified by circulating hormones. Recently, the effect of leptin on sweet-responding taste cells has generated much interest. Leptin, a protein hormone secreted mainly by adipocytes regulates body mass and suppresses insulin secretion by the activation of ATP-sensitive KCn . Its inhibitory effect on TRCs also involves the activation of a K+ conductance and membrane hyper polarization. Thereby the hormone partially blunts nerve signals indicating sweet taste, which, presumably, makes food less attractive. During starvation the production of leptin is decreased (Ref.5). The resulting disinhibition in the target tissues diminishes energy expenditure and leads to the motivational state of hunger. At the same time, disinhibition of sweet-responsive taste cells enhances sensitivity to sweet taste, making sweet food more attractive. Thus the effect of leptin on the taste system supports the general role of this hormone in regulating nutrition, body weight and energy balance.

Taste is an important part of everyones daily life. Sweet taste is particularly important as evidenced by the fact that wars have been fought and people have been enslaved over sugar, the prototypical sweet stimulus. The sensation sweet guides us to food that is rich in carbohydrates. Both protein and carbohydrates are essential nutrients, hence, evolution took care that sweet and umami evoke pleasant sensations and stimulate food uptake. This behavioural pattern is especially obvious already in new born children: if you put some sugar on their tongue, they smile and immediately start to suck. If uncontrolled, unfortunately, in our civilized world this behaviour leads to increased body weight and obesity. Considerable efforts are being made by chemists and researchers in food-producing companies to deduce from hundreds of sweet-tasting compounds common structural features that are expected to capture characteristics of the sweet molecule and, therefore, the sweet receptor.