Taste and Nutrition

Home , TAS2R31

Author's copy! Any use beyond the limits of copyright law without the consent of the publisher is prohibited and punishable. This applies in particular to duplications, transla- tions, microfilming as well as storage and processing in electronic systems. Special | Sensory Science

Peer-reviewed | Manuscript received: February 13, 2013 | Revision accepted: April 12, 2013 Taste and nutrition

1. Physiological basis of taste perception

Maik Behrens, Anja Voigt, Wolfgang Meyerhof, Potsdam-Rehbrücke

Top view of a model of the bitter receptor TAS2R10 with bound strychnine. The strychnine molecule together with three amino acid residues, which have been demonstrated to participate in agonist-selective interactions, are shown central in the binding site of the receptor. The hydrogen bond between strychnine and a serine residue at position 85 of the receptor is indicated. The gray ribbons show the locations of the receptor’s transmembrane domains. For a more detailed illustration see [19]. (Illustration: Anke LINGENAUBER, Nuthetal, based on data from [19])

Taste preferences and aversions determine what subjects eat and drink and thus impact on their health and disease risk. However, we know relatively little about the principles of how taste affects food choice. The present article discusses the physiological basis of gustation. Two future articles explain the influences of genetic variability and environmental factors on taste perception and nutrition and describe the formation of taste preferences and aversions.

124 Ernaehrungs Umschau international | 7/2013 Functional morphology of the peripheral taste system Summary

Flavor Each taste quality is represented by a specific population of oral chemosensory cells. They are equipped with special receptor molecules At least tree of our senses contribute which determine the molecular receptive ranges of the sensory cells. to the perception of food. The sense Whereas the receptors for salty and sour are, at present, not extensively of smell detects the scent of a meal characterized, a plethora of data exists for sweet, umami and bitter re- which, through sniffing, reaches the ceptors. Although sweet and bitter receptors recognize a broad range olfactory mucosa via the nostrils or of compounds, two different strategies are effective to achieve this goal. the nasopharynx. Touch and pain re- In case of the bitter receptors numerous genes have evolved, whereas port about the texture and tempera- only two genes code for subunits of the sweet taste receptor. This re- ture of food and the presence of irri- ceptor, however, possesses multiple binding sites to recognize a diversity tants that elicit hot, pungent, astrin- of sweet substances. gent, metallic, burning, tingling or electrical sensations. Taste, in the In the taste buds of the tongue sensory cells form assemblies of about true sense of the word, is restricted 100 cells, which process and integrate taste information with metabolic to the five basic tastes or taste qual- needs. Sensory afferent nerves transfer gustatory information from the ities, sweet, sour, salty, bitter, and mouth to the brainstem to evoke stereotyped innate attraction or aver- umami (savoury). The brain uses all sion and to prepare the body for digestion. The activity of nerve cells in these types of impressions to con- special areas of the cerebral cortex represents the basic tastes and gen- struct complex flavors. In the fol- erates complex flavours by integrating information about taste, smell lowing the word taste merely refers and texture of food. to the five basic taste qualities. Keywords: taste, gustation, physiology, sweet, salty, sour, bitter, umami

Taste organs

Taste buds form, foliate, and vallate papillae lial cells and not neurons. The con- The five basic tastes are elicited by based on their shape, location and ventional cell typing that is based on substances that are recognized by the number of hosted taste buds. About morphological criteria is currently taste buds. These principle taste or- 300 small, slightly elevated fungi- being replaced by functional para - gans are onion-shaped assemblies of form papillae are distributed about meters which led recently to the dis- ~ 50–100 mostly elongated cells. the anterior two thirds of the covery of a fundamental principle in With their apical tips numerous of tongue. In humans, they contain up gustation, i. e., the existence of ge- these cells contact a depression in the to five taste buds [1]. The foliate netically determined, segregated oral epithelium, referred to as taste papillae are found at the posterior populations of chemosensory cells pore, the contact site between taste edges of the tongue and form up to for the 5 basic tastes [3]. This means molecules and their receptive struc- five fissions which contain several the percept of a basic taste is equi- tures. hundred taste buds [2]. The posterior valent to the excitation of the cog- tongue displays on average nine val- nate population of oral chemosen- Taste papillae late papillae which are arranged in a sory cells. This principle explains the The majority of oral taste buds re- V-shaped manner. They possess existence of only few taste qualities sides in the lingual taste papillae most of the lingual taste buds as as well as the high discriminatory (v Figure 1A). We distinguish fungi- each of them contains several hun- power across taste qualities and the dred of these cell assemblies. Further low discriminatory power with taste taste buds are embedded in the oral qualities. The molecular receptive Citation: epithelium of the palate, epiglottis, ranges of the five taste cell popula- Behrens M, Voigt A, Meyerhof W pharynx and larynx. tions for taste compounds are de- (2013) Taste and nutrition. 1. fined and separated by the special Physiological basis of taste per- Chemosensory cells taste receptor molecules they ex- ception. Ernaehrungs Umschau in- The chemosensory cells of taste buds press. The bitter off-taste of saccha- ternational 60(7): 124–131 differ in shape and function (v Figure rin is thus a result from its ability to This article is available online: 1B) [2,3]. They are referred to as sec- potently activate the sweet sensing DOI: 10.4455/eu.3013.024 ondary sensory cells to indicate the cells and, at the same time, to fact that they are specialized epithe- weakly excite the sensory cells dedi- Ī

Ernaehrungs Umschau international | 7/2013 125 Special | Sensory Science

cated to bitter. Taste cells are very ferent fibers come particularly close. via a different type of receptor, its short-lived and replaced by cells that It is assumed that these are the sites own release from sensory cells [6]. develop from spherical progenitor of ATP release. The use of the same Furthermore, adenosine resulting cells that reside at the base of taste neurotransmitter by all of the 5 re- from the enzymatic degradation of buds [4]. ceptor cell populations raises the im- ATP, stimulates selectively the re- portant question of how the brain sponsiveness of sensory cells devoted correctly interprets the taste quali- to the recognition of sweet stimuli Detection and transmission of ties. The most attractive hypothesis [6]. This clearly indicates that taste taste stimuli to date assumes that the released ATP buds are in fact not just structures Stimulation of all types of taste re- is confined to quality specific micro which detect and transmit taste stim- ceptor cells leads to the excitation of domains in the taste buds [2], yet uli, but rather complex sensory or- afferent sensory fibers in a manner their existence remains to be demon- gans that integrate taste information dependent on the neurotransmitter strated. already in the oral cavity [2]. This ATP. This has been demonstrated in In addition to ATP, several other concept is underscored by the fact mice lacking a special type of ATP re- transmitter substances along with that taste sensitivity is dynamically ceptor [5]. Noteworthy, only the re- their corresponding receptors have modulated to fit acute metabolic receptor cells dedicated to sour form been identified in taste buds. Al- quirements. For example the counter- conventional chemical synapses, i.e., though not in all cases the specific regulatory roles of the hunger and specialized contacts between two role of these additional neurotrans- satiety hormones endocannabinoid cells that propagate the excitation mitters was demonstrated unam- and leptin, respectively, modify the from cell to cell. However, it remains biguously, evidence is mounting that sensitivity of sweet taste receptor unknown if sour sensing cells they serve functions in the commu- cells in opposite directions [7]. synaptically release ATP [2]. The cells nication between sensory cells. The for sweet, bitter and umami stimuli released ATP for example, not only Neuroanatomy do not form synapses. However, elicits action potentials in the affer- they have specializations where af- ent nerve fibers, but also stimulates, Taste information originating from the oral cavity is transmitted to the brainstem via three cranial nerves A C (v Figure 1C) [8]. Contacts with other nerve cells residing in this brain re- GC vallate papilla gion mediate muscle contractions co- TH ordinating tongue movement, chew- ing and swallowing to facilitate the foliate papilla ingestion of digestible food items and the disgorging of potentially harmful substances. Furthermore, taste in- fungiform papilla VII. B NTS formation prepares the alimentary oral cavity tract in advance for the digestion of epithelium sweet IX. umami taste receptor the food [9]. The brainstem wires salty cells sour X. taste information via the midbrain to bitter a specialized area within the cere- supporting cell gustatory precursor cell nerves brum, the gustatory cortex. Here, the connective tissue nerve fibers conscious perception of the basic taste qualities is reflected by nerve activity patterns. Together with infor- Figure 1: Anatomy of the taste system mation about the smell and textural (A) Schematic of the location and morphology of the three types of taste papillae. The taste buds are embedded in the mucosa of protrusions or in- properties of the consumed food a vaginations of taste papillae. (B) The onion-shaped appearance of taste complex flavor percept is generated. buds is caused by numerous elongated cells. Note that for each of the five Flavor recognition, in turn, is indis- basic taste qualities a separate cell population exists. (C) Branches of three pensable for the development of food cranial nerves (VII., IX., X.) innervate the taste buds and transmit taste in- preferences and aversions. Further formation to the Nucleus tractus solitarius (NTS), a part of the brainstem. The cell bodies of the three nerves are located in ganglia outside the brain. brain areas involved in the process- The NTS relays taste information via the thalamus (TH) to the gustatory ing of taste information include re- cortex (GC). (Illustration: Jonas TÖLE, Nuthetal) gions that regulate intake of nutri-

126 Ernaehrungs Umschau international | 7/2013 ents and liquids as well as reward A functional TAS1-receptor consists The sweet taste receptor TAS1R2/3 systems involved in the generation of of two different subunits. Whereas is the universal sensor for all sub- addictive behaviors [1]. the TAS1R1 and TAS1R3 subunits stances eliciting a sweet taste percep- assemble to form the umami reception. Given the large number of The receptors for sweet, tor [11], the sweet taste receptor sweet tasting substances, this is an umami, and bitter taste consists of the TAS1R2 and TAS1R3 enormous task to fulfill. On top of subunits [12]. Hence, both receptors the prototypical sweet tastants such perception share the TAS1R3 subunit and pos- as mono- and disaccharides (v Table The tasks for sweet and umami taste sess one specific subunit each. On a 1), numerous natural and synthetic receptors on the one hand, and that cellular level this principle is evident compounds activate this receptor. of bitter taste receptors on the other by the observed co-expression of the Perhaps one of the most important hand couldn’t be more different. TAS1R3 gene with either of the findings of recent research concern- Whereas sweet and umami receptors TAS1R1 or TAS1R2 genes, but a ing the sweet taste receptor is the are tailored for the detection of the strict separation of TAS1R1 and characterization of individual bind- building blocks for the universal TAS1R2 gene expression. ing sites of various sweet tastants in macronutrients, carbohydrates and proteins, bitter taste receptors are re- quired to respond to a large variety Receptor Agonists of potentially harmful toxic food in- umami gredients. For these very different TAS1R1/R3 L-glutamic acid, enhanced by 5’-ribonucleoside phosphate tasks nature has chosen its perhaps sweet most versatile tools, the G protein- TAS1R2/R3 Mono-/disaccharides, coupled receptors (GPCRs). Numer- plant sweet proteins (e.g. brazzein, thaumatin), artificial ous hormone and neurotransmitter sweeteners (e.g. saccharin, aspartame), natural sweeteners (e. g. steviosides) receptors, but also the visual pig- ment, rhodopsin, belong to this class bitter of molecules. TAS2R1 Humulones TAS2R3 Chloroquine TAS1Rs TAS2R4 Colchicin, L-tryptophane, D-tryptophane TAS2R5 1,10-Phenanthrolin The family of TAS1R (taste receptor, type 1) genes is responsible for rec- TAS2R7 caffeine ognizing the taste qualities sweet TAS2R8 Chloramphenicol and umami (for a recent review arti- TAS2R9 Ofloxazin cle see [10]). Based on their amino acid sequence and structural simi- TAS2R10 Parthenolide, denatonium benzoate, strychnine larities the three members of this TAS2R13 Diphenidol, denatonium benzoate gene family, TAS1R1, -R2 and –R3, TAS2R14 picrotoxinin, aristolochic acid, caffeine, absinthin belong to the class C of GPCRs. This receptor class is characterized by TAS2R16 D-(-)-salicin, D-arbutin, amygdalin long, amino terminally located ex- TAS2R20 Cromolyn tracellular domains. They form a TAS2R30 Denatonium benzoate, Picrotoxinin structure resembling the traps of the plant Venus flytrap (“venus flytrap TAS2R31 Aristolochic acid, saccharin, acesulfame K motif”). The carboxy terminal part TAS2R38 Phenylthiocarbamide (PTC), 6-n-propylthiouracil (PROP) of these proteins with its 7 trans- TAS2R39 Quinine, thiamin, amarogentin membrane domains that are con- TAS2R40 Humulones, quinine nected via 3 intra- and 3 extracellular loops, however, takes the shape TAS2R43 Aristolochic acid, saccharin, acesulfame K of a typical GPCR. Between the TAS2R46 strychnine, absinthin, parthenolide amino terminal Venus flytrap motif TAS2R50 Amarogentin, andrographolide and the transmembrane region an additional, cystein-rich domain is Table 1: Human taste receptors and some of their activators present. TAS1R/TAS2R = tast receptor, type 1/2 Ī

Ernaehrungs Umschau international | 7/2013 127 Special | Sensory Science

different parts of this receptor (v Fi- TAS1R1/3, much fewer activating these bitter taste receptor cells ex- gure 2). A key finding for the suc- molecules have been identified. press on average only 4-11 different cessful identification of these binding Whereas the human umami recep- TAS2R genes, the population of sites has been the observation of tor is specifically tailored for the human bitter taste receptor cells is species-specific differences in sweet recognition of L-glutamate, the cor- highly heterogeneous [16]. In con- taste perception. Whereas many ar- responding rodent receptor is acti- trast to the already described tificial sweet compounds activated vated by additional L-amino acids TAS1Rs, TAS2Rs exhibit only very the human sweet taste receptor, the [11]. A common hallmark of the short extracellular amino termini corresponding rodent receptors do human as well as the rodent umami (v Figure 2) and, due to their low not respond to many of these sub- receptor is a strong, ~30-fold en- amino acid sequence relationship stances [12,13]. Through the smart hancement of its sensitivity by ino- with other GPCRs, are difficult to be combination of subunits from dif- sine monophosphate (IMP) and other grouped into existing GPCR-subfam- ferent species or parts thereof and 5-ribonucleotides such as GMP. ilies. subsequent functional in vitro exper- One of the most burning questions iments it was possible to locate these TAS2Rs in bitter taste research has been, how binding sites. These experiments a rather small number of TAS2Rs demonstrated that the sweet taste re- There are countless of structurally may possibly suffice to detect hun- ceptor possesses several binding sites diverse bitter compounds present in dreds of diverse bitter compounds? for sweet compounds distributed nature. Many of these possess con- The enormous progress made in the over different parts of the molecule siderable pharmacological activities identification of activators for the 25 and, moreover, provided a convinc- and hence could be harmful if in- human TAS2Rs (a process called “de- ing explanation for the apparent dis- gested. The perception of all these orphanization” because previously crepancy between the number and potentially toxic substances is medi- “orphan” receptors become associ- diversity of sweet compounds and ated by the bitter taste receptors of ated with cognate activators) has the existence of only a single sensor the TAS2R (taste receptor, type 2) provided important results to an- for these compounds. The identified gene family [14,15]. Humans pos- swer this question (v Table 1). binding sites are located in the Venus sess 25 of these receptors, whereas flytrap domains of both subunits, other mammals can have more (e.g. In the course of these experiments, the transmembrane region of the mouse with 35) or fewer (e.g. horses which resulted in the successful de- TAS1R3 as well as within the cys- with 19) TAS2R genes. orphanization of, so far, 21 of the 25 tein-rich domain. Bitter taste receptor genes in the oral human TAS2Rs, it was shown that cavity are expressed in a separate the breadth of agonist spectra of In contrast to the sweet taste recep- population of taste sensors, the bit- these receptors deviate considerably. tor, for the umami receptor, ter taste receptor cells. Since each of Some receptors, the “generalist” receptors, exhibit an extremely broad agonist spectrum, the “specialist” re- umami receptor sweet receptor bitter receptor ceptors respond only to few agonists, whereas the majority of receptors showed an intermediate breadth of tuning [17]. The three most broadly tuned receptors, TAS2R10, - R14, and –R46, each respond to about one-third of all tested bitter compounds and their combined agonist spectra are sufficient for the

TAS1R1 TAS1R3 TAS1R2 TAS1R3 TAS2R recognition of already half of all bitter substances. On the other extreme, the receptors TAS2R3, -R5, -R13, - Figure 2: Schematic of sweet, umami, and bitter receptor structures R20, and -R50 are activated by only The extracellular Venus flytrap motifs of the TAS1R are shown. The very few bitter substances. Intri- cystein-rich domains of TAS1Rs are highlighted as bold lines. Trans- guingly, even the most broadly tuned membrane helices are shown as cylinders traversing the plasma membrane. Identified binding sites for activators are indicated by TAS2Rs possess only a single ligand gray spheres. (Illustration: Authors’ own schematic) binding pocket (v cover illustration), TAS1R/TAS2R = taste receptor, Type 1/2 which accommodates all the diverse

128 Ernaehrungs Umschau international | 7/2013 bitter compounds via different con- sweet and umami receptors on the receptor in the endoplasmic reticu- tact points between receptor and ag- one hand, and bitter receptors on the lum causing elevation of intracellu- onists [18]. other hand, the signal transduction lar calcium levels. The calcium-in- mechanism is similar (v Figure 3). duced opening of the ion channel Moreover, it has been demonstrated Activation of the receptors is trans- TRPM5 initiates a kation current that the ligand binding pockets are mitted via a specific heterotrimeric through the plasma membrane, re- tailored to accommodate numerous guanine nucleotide binding protein sulting in the depolarization of taste compounds at the expense of possi- onto the enzyme phospholipase C 2. receptor cells and the concurrent re- bly higher affinities for each of the The resulting inositol-1,4,5-tris - lease of the neurotransmitter ATP single substances [19]. Two of the 25 phosphate stimulates the type 3 IP3- through pannexin-hemichannels. human TAS2Rs exhibit pronounced selectivity for distinct large classes of bitter compounds. One of them is the TAS2R16, which responds al- most exclusively to stimulation with sweet-, umami-, bitter receptor β-D-glucopyranosides, the other receptor, the TAS2R38, is activated only by molecules possessing iso - heterotrimeric G Protein thiocyanate or thioamide groups. All Gα-gustducin, Gβ3(1), Gy13 other receptors exhibit intermediate tuning properties.

In summary, the deorphanization phospholipase Cβ2 process allowed to clarify the question of how so few receptors can possibly be responsible to facilitate recog- inositol-1,4,5-trisphosphate nition of so many different bitter compounds. In fact, the question can now be turned around and one may ask why do humans possess so many IP3-receptor receptors with, in part, clearly overlapping agonist spectra? The recent identification of naturally occurring calcium ions bitter taste receptor inhibitors may provide an explanation for this phe- nomenon [20]. These inhibitors are present in the same plants synthesiz- TRPM5 channel ing typical bitter compounds, however, unlike agonists they block bitter receptor responses instead of activat- cell depolarization ing them. The presence of multiple receptors with overlapping agonist in- teraction patterns may prevent the complete inhibition of bitter taste pannexin hemichannel recognition by such substance and thus, prevent the accidental ingestion of those plants with possibly fatal neurotransmitter ATP consequences.

Intracellular signaling cascades of Figure 3: Flow diagram of the cellular signal transduction cascade in TAS1Rs and TAS2Rs taste receptor cells Despite of the obvious differences in The single components are shown following the sequence of their activation. Abbreviations: IP3-receptor, inositol-1,4,5-trisphosphate structure, number, activation mech- receptor; TRPM5, transient receptor potential cation channel sub- anisms and their strict separation in family M, member 5; ATP, adenosine trisphosphate (Authors’ own different cell populations among diagram). Ī

Ernaehrungs Umschau international | 7/2013 129 Special | Sensory Science

Sour transduction Salt taste transduction remains unknown. The amiloride- insensitive salt taste involves other Acids are the principle stimuli of We continuously loose electrolytes transduction mechanisms. Appar- sour taste. Since strong inorganic through excretion. In this context ently, high-salt-reception recruits acids such as hydrochloric acid dis- salty taste can be considered a con- sour and bitter transduction path- sociate completely in protons and trol element ensuring electrolyte ways [24] which impressively ex- anions, we have to assume that pro- homeostasis. The recognition of salt plains the unpleasant sensation that tons themselves serve as sour stim- and its intrinsic pleasant taste at low is evoked by high sodium concentra- ulus. But also weak organic acids to moderate concentrations pro- tions and other mineral salts. taste sour. Paradoxically, at constant motes salt uptake compensating the pH the weak acetic acid appears to be continued loss. Comparatively, little is known about sourer than the strong hydrochloric Salty taste is mostly elicited by NaCl, salt taste in humans. It is true that acid [6]. This led to the assumption table salt, but other sodium salts the ENaC subunits are present in that, in addition to protons, the elicit a very similar taste. The taste human taste buds but salt taste in undissociated organic acids serve as of other mineral salts does not com- humans is amiloride insensitive [25] adequate sour stimuli [21]. In the pare to the taste of NaCl, it is clearly challenging a potential role for ENaC protonated state organic acids are ca- different. in human salt transduction. Perhaps pable of permeating plasma mem- the insensitivity of human salt taste branes. In the cytosol they dissociate In rodents two salt tastes have been to amiloride can be explained by a described. One of them is pleasant into protons and anions which leads different channel composition. Hu- and specifically elicited by sodium to intracellular acidification. mans possess an additional ENaC ions. This taste is induced by low gene which is absent in rodents and stimulus concentrations and blocked which encodes the δ-subunit. Delta- Receptor candidates for sour have re- by the diuretic drug amiloride. The ENaC is also present in human taste peatedly been reported about in the other is repulsive, depends on high buds and can functionally replace literature. To date, none of them sodium concentration, is also elicited the α-subunit. However, δ-ENaC is matches all of the necessary criteria by various other mineral salts in- far less sensitive to amiloride than that a true sour receptor should ful- cluding calcium, magnesium, am- the α-subunit [26] which could ex- fill. Despite this lack of knowledge monium and potassium salts, and plain the amiloride-insensitivity of we have to assume that at least two insensitive to amiloride. The obser- human salty taste. However, future transduction pathways are involved vation that rodents are unable to dis- research has to clarify this and other in the recognition of acids [2]. tinguish NaCl from KCl in the pres- open questions regarding sour and Plasma membrane proton channels ence of amiloride illustrates the du- salty transduction. enable the influx of protons into the alism of salty taste [22]. cytosol of sour-detecting receptor A well-known target for amiloride in Outlook cells in the taste bud. Together with the kidney is ENaC, the epithelial those protons released from the or- sodium channel which is composed We have seen that important con- ganic acids in the cytosol they acti- of two alpha, a beta and a gamma cepts and basic principles in taste vate intracellular target sites. Even- subunit. The ENaC is highly selective perception have been worked out tually this leads to calcium influx in for sodium ions and mediates the re- quite recently. However, new know- the sour-detecting sensory cells and covery of sodium from the primary ledge raises new questions. Thus, we release of neurotransmitter sub- urine. These findings led to the as- have to register unexpected large stances. This hypothesis is also sup- sumption that ENaC in oral taste tis- gaps in our knowledge about sour ported by the observation that all sues is involved in salt transduction. and salty taste and about funda- taste cells are accessible to organic Various circumstantial evidence sup- mental principles of gustatory infor- acids and show the drop in pH but ported this assumption, yet only mation transmission from mouth to only in the sour receptor cells low very recent direct evidence demon- brain. Moreover, taste receptors have pH is coupled to calcium influx and strated that α-ENac is part of the salt recently been found in numerous ex- neurotransmitter release [6]. transduction machinery [23]. How- traoral sites where they probably ever, the precise channel composition exert hitherto unknown functions.

130 Ernaehrungs Umschau international | 7/2013 Numerous laboratories world- References wide aim at filling the gaps in knowledge. In particular, eluci- 1. Smith DV, Boughter JD, Jr. Neurochemistry of 16. Behrens M, Foerster S, Staehler F et al. (2007) dating the molecular and cellu- the Gustatory System. In: Lajtha A, Johnson Gustatory expression pattern of the human lar basis of gustatory transmis- DA (ed). Handbook of Neurochemistry and Mo- TAS2R bitter receptor gene family reveals a het- sion and processing in the brain lecular Neurobiology. Springer, New York erogenous population of bitter responsive taste is indispensable for understand- (2007), S. 109–135 receptor cells. J Neurosci 27: 12630–12640 ing of how taste impacts on in- 2. Roper SD (2007) Signal transduction and in- 17. Meyerhof W, Batram C, Kuhn C et al. (2010) gestive behavior. The to-do-list formation processing in mammalian taste The molecular receptive ranges of human TAS2R for taste researcher is long and buds. Pflugers Arch 454: 759–776 bitter taste receptors. Chem Senses 35: 157–170 complex and hopefully can be 3. Chandrashekar J, Hoon MA, Ryba NJ et al. 18. Brockhoff A, Behrens M, Niv MY et al. (2010) worked off quick in order to (2006) The receptors and cells for mammalian Structural requirements of bitter taste receptor solve public health issues in nu- taste. Nature 444: 288–294 activation. Proc Natl Acad Sci U S A 107: trition some of which will be 4. Beidler LM, Smallman RL (1965) Renewal of 11110–11115 targeted in the next articles. cells within taste buds. J Cell Biol 27: 263–272 19. Born S, Levit A, Niv MY et al. (2012) The 5. Finger TE, Danilova V, Barrows J et al. (2005) Human Bitter Taste Receptor TAS2R10 Is Tai- ATP signaling is crucial for communication lored to Accommodate Numerous Diverse Lig- from taste buds to gustatory nerves. Science ands. J Neurosci 33: 201–213 310: 1495–1499 20. Brockhoff A, Behrens M, Roudnitzky N et al. Acknowledgement 6. Roper SD (2013) Taste buds as peripheral (2011) Receptor agonism and antagonism of di- The authors thank Jonas TÖLE chemosensory processors. Semin Cell Dev Biol etary bitter compounds. J Neurosci 31: 14775– (Nuthetal) for preparing fig- 24: 71–79 14782 ure 1 and Anke LINGENAUBER 7. Jyotaki M, Shigemura N, Ninomiya Y (2010) 21. Lyall V, Alam RI, Phan DQ et al. (2001) De- (Nuthetal) for the preparation Modulation of sweet taste sensitivity by orexi- crease in rat taste receptor cell intracellular pH of the cover illustration based genic and anorexigenic factors. Endocr J 57: is the proximate stimulus in sour taste trans- on data from [19]. 467–475 duction. Am J Physiol Cell Physiol 281: C1005– 8. Hamilton RB, Norgren R (1984) Central projec- C1013 tions of gustatory nerves in the rat. J Comp 22. Eylam S, Spector AC (2005) Taste discrimina- Neurol 222: 560–577 tion between NaCl and KCl is disrupted by 9. Spector AC (2000) Linking gustatory neurobi- amiloride in inbred mice with amiloride-insen- ology to behavior in vertebrates. Neurosci Biobe- sitive chorda tympani nerves. Am J Physiol Dr. Maik Behrens1 hav Rev 24: 391–416 Regul Integr Comp Physiol 288: R1361–R1368 Dr. Anja Voigt2 Prof. Dr. Wolfgang Meyerhof3 10. Behrens M, Meyerhof W, Hellfritsch C et al. 23. Chandrashekar J, Kuhn C, Oka Y et al. (2010) German Institute of Human Nutrition (2011) Sweet and umami taste: natural prod- The cells and peripheral representation of (DIfE) Potsdam-Rehbrücke, ucts, their chemosensory targets, and beyond. sodium taste in mice. Nature 464: 297–301 Arthur-Scheunert-Allee 114–116, Angew Chem Int Ed Engl 50: 2220–2242 24. Oka Y, Butnaru M, von Buchholtz L et al. 14558 Nuthetal, Germany; 11. Nelson G, Chandrashekar J, Hoon MA et al. (2013) High salt recruits aversive taste path-

1E-Mail: [email protected] (2002) An amino-acid taste receptor. Nature ways. Nature 494: 472-475 2E-Mail: [email protected] 416: 199–202 25. Staehler F, Riedel K, Demgensky S et al. (2008) 3E-Mail: [email protected] 12. Nelson G, Hoon MA, Chandrashekar J et al. A Role of the Epithelial Sodium Channel in Conflict of Interests (2001) Mammalian sweet taste receptors. Cell Human Salt Taste Transduction? Chem Percept Maik BEHRENS has filed patents and pa- 106: 381–390 1(1): 78–90 tent applications on human bitter taste. 13. Li X, Staszewski L, Xu H et al. (2002) Human 26. Halpern BP (1998) Amiloride and vertebrate Anja VOIGT declares no conflict of interest receptors for sweet and umami taste. Proc Natl gustatory responses to NaCl. Neurosci Biobehav in accordance with the guidelines of the Acad Sci U S A 99: 4692–4696 Rev 23: 5–47 International Committee of Medical Jour- 14. Adler E, Hoon MA, Mueller KL et al. (2000) A nal Editors. novel family of mammalian taste receptors. Cell Prof. Dr. Wolfgang MEYERHOF filed several 100: 693–702 patents and patent applications on bitter receptors. Parts of his research are fun- 15. Chandrashekar J, Mueller KL, Hoon MA et al. (2000) T2Rs function as bitter taste receptors. ded by industrial partners. DOI: 10.4455/eu.2013.024 Cell 100: 703–711

Ernaehrungs Umschau international | 7/2013 131