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A matter of taste Teaching in medical school can, as many of us know, be a burden and an enormous privilege at the same time (while all the time you wonder how it is that medical students become younger and younger these days). It is a truly elating experience to see the eyes of a student light up with understanding, sometimes you ght like Don Quichote against the windmills of bureaucracy, and sometimes questions in class send you back to the library. Lately, one of the lectures on satiety regulation prompted a discussion about the physiological background vs. the philosophical denition of hunger and appetite, of food aversion and craving and of the role of the human sensory systems, especially taste, in what we actually mean when we say that we like something. We saw classroom discussions followed by chat forum articles posted at 2 a.m. on a topic we would not have expected to be perceived by our students as that sexy, and were taught otherwise. Lets have a look at the current research results on taste coding and taste receptor signalling, which has recently been featured in some excellent articles in Acta Physiologica (Oxford). Taste lets us evaluate the potential (i) nutritional value and/or (ii) toxic quality of a substance. Taste buds, discovered by Christian Love n of the Karolinska Intstitute in the 18th century (Persson 2012), are distributed to the papillae on the tongue, palate, uppermost oesophagus and epiglottis, and this is where taste sensations start. As is common knowledge, we rely on a surprisingly small number of modalities: sweet to let us know where carbohydrates are to be found, umami (savoury) for certain amino acids, sour and bitter to warn us from poison and salty to attract us to the electrolytes that supposedly were rare in times when humans evolved. Taste sensation relies on two transduction principles: Apical ion channels for salty and sour tastes (i.e. the sensation of Na+ or H+ ions) and G-proteincoupled taste receptor complexes (GPCR) with their respective downstream second-messenger cascades for sweet, umami and bitter (Kinnamon 2012). Recent research results, especially using transgenic technology, have revealed interesting details. First, the attractive tastes sweet and umami utilize a combination of two out of only three GPCRs, named T1R13. The sweet receptor is a T1R2+3 heterodimer, which, in mammals, interestingly responds not only to natural sugars, but also to sweeteners, certain amino acids and even proteins (Chandrashekar et al. 2006). To this end, the receptor complex uses different intramolecular domains. Species-specic response proles apparently rely on T1R sequence differences. Feline species carry a loss-of-function mutation in T1R2, which renders them unable to taste sweet (Li et al. 2005). T1R1+T1R3 form the umami or savoury receptor, another attractive modality which apparently shares an evolutionary origin with the sweet receptor, and which reacts to a variety of L-amino acids in mammals. Only in humans, it is specically stimulated by aspartate and monosodium glutamate (MSG). Especially the latter has been at the focus of many a discussion recently, being blamed for the Chinese restaurant syndrome (Williams & Woessner 2009) and for causing overeating and obesity (He et al. 2011). The term taste ination was coined in the lay literature to denote the ingestion of food that is overly rich in sugar, salt and MSG in the modern Western diet, blamed with desensitizing the taste and necessitating ever-increasing quantities of according food components (Adams 2005). Undoubtedly, taste preferences are the consequence of predisposition and (early) food experiences (Lipchock et al. 2011), and are culturally shaped. Interestingly, the Roman Empire already saw heated discussions on the use of glutamic acid highly contained in garum, a condiment loved and consumed by the masses (Curtis 2009), but dismissed as vulgar and harmful by the educated elite (Seneca n.d., Epistle 95). Large-scale reviews of blinded trials have shown no consistent evidence to suggest that individuals may be uniquely sensitive to MSG (Freeman 2006, Williams & Woessner 2009). Bitter taste is perceived by the highly diverse T2R family, and often many different members are expressed on one cell, apparently, to rather provide a broadly tuned sensor (Chandrashekar et al. 2006) then discrimination, to warn us of poison. The TXR downstream pathway via heterodimeric G-proteins, PLC2, IP3/DAG and gating of the taste-transducing channel TRPM5 seems to be a common one among the different cells that express the different TXR family members (Kukkonen 2012). Transient receptor potential proteins, as many of their family members, function here as mediators of a variety of sensations, and their presence indicates that modulation by cotransmitters, metabolic products or physical inuences such as temperature seems at least possible (Beech

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Acta Physiol 2013, 207, 203205

(a)

(b)

(c)

sensory organs in what appears to be a most complex, nely tuned and behaviourally modulated manner (Spector & Travers 2005), with newly developed imaging techniques allowing us ever more insight (Lecrux & Hamel 2011). Obtaining chemosensory information about nutrients, however, is not limited to taste, but occurs widely in the GI tract (Iwatsuki et al. 2012, Akiba & Kaunitz 2011), for example, for acids (Holzer 2011, Sjo blom 2011, Dong et al. 2011). Airway bitter receptors trigger defensive reexes (Kinnamon 2012). Interestingly, animals such as amphibiae express receptor structures comparable to the human taste sensation on their skin (Hillyard & Willumsen 2011, Larsen 2011). A couple of days after coming back to the classroom and telling the students, as Hamlet once did, that There are more things in heaven and earth, Horatio, than are dreamt of in your philosophy, I received three applications for undergraduate research projects in the physiology lab. Teaching in medical school can indeed be an enormous privilege.

Figure 1 Models of peripheral encoding of gustation. According to the across-bre models, either the taste receptor cells respond to various modalities (a), or one nerve bre is connected to more than one receptor cell which responds to one taste modality (b). In both cases, activity patterns are postulated to encode the perceived modalities. In the so-called labelled-line model, one receptor cell responds to one taste modality and signals via an individual bre (c) (Chandrashekar et al. 2006).

Conict of Interest
None.

P. B. Persson and A. Bondke Persson Institute of Vegetative Physiology, Charite -Universitaetsmedizin Berlin, Berlin, Germany E-mail: anja.bondke@charite.de References
Adams, M. 2005. Taste ination revealed: why sugar, salt and fragrance make you stupid (www document). Available at: http://www.naturalnews.com/012556_taste_ina tion_processed_foods.html (accessed September 13, 2012). Akiba, Y. & Kaunitz, J.D. 2011. Luminal chemosensing in the duodenal mucosa. Acta Physiol (Oxf) 201, 7784. Beech, D.J. 2012. Integration of transient receptor potential canonical channels with lipids. Acta Physiol (Oxf) 204, 227237. Chandrashekar, J., Hoon, M.A., Ryba, N.J. & Zuker, C.S. 2006. The receptors and cells for mammalian taste. Nature 444, 288294. Curtis, R.I. 2009. Umami and the foods of classical antiquity. Am J Clin Nutr 90, 712S718S. Dong, X., Ko, K.H., Chow, J., Tuo, B., Barrett, K.E. & Dong, H. 2011. Expression of acid-sensing ion channels in intestinal epithelial cells and their role in the regulation of duodenal mucosal bicarbonate secretion. Acta Physiol (Oxf) 201, 97107. Evans, D.H. 2011. Freshwater sh gill ion transport: August Krogh to morpholinos and microprobes. Acta Physiol (Oxf) 202, 349359.

2012, Talavera et al. 2005). Salty and sour sensations, however, are currently believed to be transmitted by direct apical Na+ or H+ ion channel opening. Amiloridesensitive sodium channels, which usually help maintain body salt and water homeostasis (Evans 2011), are also involved in tasting salt, while the picture is less clear for acid taste: without the TRP channel PKD2L1, which is involved in other pH-sensing systems in the body, sour taste is not perceived; however, nucleotide-gated channels and diverse populations of H+-gated K+ and other acid-sensing channel proteins have been suggested (Chandrashekar et al. 2006). Purinergic signalling has repeatedly been postulated to be involved in taste signal transmission (Novak 2011, Iwatsuki et al. 2012) from chemical information to gustatory or vagus nerves. Although taste receptor anatomy and function have been described in much detail, the jury is still out on how they are wired to peripherally encode the taste qualities (Fig. 1; Chandrashekar et al. 2006). However, recent research has rendered the labelled-line model of peripheral taste quality encoding the most likely one (Chandrashekar et al. 2006). Taste perception is integrated with input from other 204

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Acta Physiol 2013, 207, 203205 Freeman, M. 2006. Reconsidering the effects of monosodium glutamate: a literature review. J Am Acad Nurse Pract 18, 482486. He, K., Du, S., Xun, P., Sharma, S., Wang, H., Zhai, F. & Popkin, B. 2011. Consumption of monosodium glutamate in relation to incidence of overweight in Chinese adults: China Health and Nutrition Survey (CHNS). Am J Clin Nutr 93, 13281336. Hillyard, S.D. & Willumsen, N.J. 2011. Chemosensory function of amphibian skin: integrating epithelial transport, capillary blood ow and behaviour. Acta Physiol (Oxf) 202, 533548. Holzer, P. 2011. Acid sensing by visceral afferent neurones. Acta Physiol (Oxf) 201, 6375. Iwatsuki, K., Ichikawa, R., Uematsu, A., Kitamura, A., Uneyama, H. & Torii, K. 2012. Detecting sweet and umami tastes in the gastrointestinal tract. Acta Physiol (Oxf) 204, 169177. Kinnamon, S.C. 2012. Taste receptor signalling from tongues to lungs. Acta Physiol (Oxf) 204, 158168. Kukkonen, J.P. 2012. International symposium on G-proteincoupled receptors (GPCRs), TRP (ion) channels and lipid signalling GPCR-Helsinki 2010. Acta Physiol (Oxf) 204, 148150. Larsen, E.H. 2011. Reconciling the Krogh and Ussing interpretations of epithelial chloride transport presenting a novel hypothesis for the physiological signicance of the passive cellular chloride uptake. Acta Physiol (Oxf) 202, 435464. Lecrux, C. & Hamel, E. 2011. The neurovascular unit in brain function and disease. Acta Physiol (Oxf) 203, 4759. Li, X., Li, W., Wang, H., Cao, J., Maehashi, K., Huang, L., Bachmanov, A.A., Reed, D.R., Legrand-Defretin, V.,

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Beauchamp, G.K. & Brand, J.G. 2005. Pseudogenization of a sweet-receptor gene accounts for cats indifference toward sugar. PLoS Genet 1, 2735. Lipchock, S.V., Reed, D.R. & Mennella, J.A. 2011. The gustatory and olfactory systems during infancy. Clin Perinatol 38, 627641. Novak, I. 2011a. Purinergic signalling in epithelial ion transport: regulation of secretion and absorption. Acta Physiol (Oxf) 202, 501522. Persson, P.B. 2012. Carl Friedrich Wilhelm Ludwig, a fabled physiologist and mentor of Scandinavian Physiology Announcing the Carl Ludwig Award for young authors in Acta Physiologica (Oxford). Acta Physiol (Oxf) 204, 289290. Seneca, L.A. n.d. Moral letters to Lucilius. Letter 95: On the usefulness of basic principles. (www document). http://en.wiki source.org/wiki/Moral_letters_to_Lucilius/Letter_95 (accessed September 13, 2012). Sjo blom, M. 2011. Duodenal epithelial sensing of luminal acid: role of carbonic anhydrases. Acta Physiol (Oxf) 201, 8595. Spector, A.C. & Travers, S.P. 2005. The representation of taste quality in the mammalian nervous system. Behav Cogn Neurosci Rev. 4, 143191. Talavera, K., Yasumatsu, K., Voets, T., Droogmans, G., Shigemura, N., Ninomiya, Y., Margolskee, R.F. & Nilius, B. 2005. Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 438, 10221025. Williams, A.N. & Woessner, K.M. 2009. Monosodium glutamate allergy: menace or myth? Clin Exp Allergy 39, 640646.

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