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Amino acid sensing in the gastrointestinal tract

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Abstract

Rapid progress in gastroenterology during the first part of the last century has shown that gastrointestinal (GI) function is regulated by neuroendocrine, paracrine and endocrine signals. However, recent advances in chemical sensing, especially in the last decade, have revealed that free l-amino acids (AA), among other nutrients, play a critical role in modifying exocrine and endocrine secretion, modulating protein digestion, metabolism and nutrient utilization, and supporting the integrity and defense of the GI mucosa. Many of the mechanisms by which AAs elicit these functions in the GI has been linked to the traditional concept of hormone release and nervous system activation. But most these effects are not direct. AAs appear to function by binding to a chemical communication system such as G protein-coupled receptors (GPCRs) that activate signaling pathways. These intracellular signals, although their molecular bases are not completely elucidated yet, are the ones responsible for the neuronal activity and release of hormones that in turn regulate GI functions. This review aims to describe the distribution of the known GPCRs from the class 3 superfamily that bind to different kinds of AA, especially from the oropharyngeal cavity to the stomach, what kind of taste qualities they elicit, such as umami, bitter or sweet, and their activity in the GI tract.

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Abbreviations

AA:

Amino acids

CaSR:

Extracellular calcium-sensing receptor

ECL:

Enterochromaffin-like cells

GI:

Gastrointestinal

GPCRs:

G protein-coupled receptors

HEK:

Human embryonic kidney (cells)

mGluR1:

Metabotropic glutamate receptor type 1

mGluR4:

Metabotropic glutamate receptor type 4

NO:

Nitric oxide

5-HT:

Serotonin

References

  • Adibi SA, Mercer DW (1973) Protein digestion in human intestine as reflected in luminal, mucosal, and plasma amino acid concentrations after meals. J Clin Invest 52:1586–1594

    Article  PubMed  CAS  Google Scholar 

  • Agostini C, Carratu B, Boniglia C, Riva E, Sanzini E (2000) Free amino acid content in standard infant formulas: comparison with human milk. J Am Coll Nutr 19:434–438

    Article  Google Scholar 

  • Akiba Y, Watanabe C, Mizumori M, Kaunitz JD (2009) Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats. Am J physiol Gastrointest Liver Physiol 297:G781–G791

    Article  PubMed  CAS  Google Scholar 

  • Bachmanov AA, Beauchamp GK (2007) Taste receptor genes. Annu Rev Nutr 27:389–414

    Article  PubMed  CAS  Google Scholar 

  • Beauchamp GK, Maller O, Roger JG (1977) Flavor preferences in cats (Felis catus and Panthera sp.). J Comp Physiol 91:1118–1127

    CAS  Google Scholar 

  • Bellisle F, Monneuse MO, Chabert M, Laure-Achagiotis C, Latenaume MT, Louis-sylvestre J (1991) Monosodium Glutamate as a palatability enhancer in the European diet. Physiol Behav 49:869–873

    Article  PubMed  CAS  Google Scholar 

  • Bezecon C, le Coutre J, Damak S (2007) Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem Senses 32:41–49

    Article  Google Scholar 

  • Birch GG, Kemp S (1989) Apparent specific volumens and tastes of amino acids. Chem Seses 14:249–258

    Article  CAS  Google Scholar 

  • Blackshaw LA, Brookes SJ, Grundy D, Schemann M (2007) Sensory transmission in the gastrointestinal tract. Neurogastroenterol Motil 19:1–19

    Article  PubMed  CAS  Google Scholar 

  • Brown EM, MacLeod RJ (2001) Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 1:239–297

    Google Scholar 

  • Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC (1993) Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 366:575–580

    Article  PubMed  CAS  Google Scholar 

  • Busque SM, Kerstetter JE, Geibel JP, Insogna K (2005) L-type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells. Am J Physiol Gastrointest Liver Physiol 289:G664–G669

    PubMed  CAS  Google Scholar 

  • Bystrova MF, Romanov RA, Rogachevskaja OA, Churbanov GD, Kolesnikov SS (2010) Functional expression of the extracellular-Ca2+-sensing receptor in mouse taste cells. J Cell Sci 123(Pt6):972–982

    Google Scholar 

  • Caplice E, Fitzgerald GF (1999) Food fermentations: role of microorganisms in food production and preservation. Int J Food Microbiol 50:131–149

    Article  PubMed  CAS  Google Scholar 

  • Caspary WF (1992) Physiological and pathophysiology of instestinal absorption. Am J Clin Nutr 55(1 Suppl):299S–308S

    PubMed  CAS  Google Scholar 

  • Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ (2000) T2Rs functions as bitter taste receptors. Cell 6:703–711

    Article  Google Scholar 

  • Chandrashekar J, Kuhn C, Oka Y, Yarmolinsky DA, Hummler E, Ryba NJ, Zuker CS (2010) The cells and peripheral representation of sodium taste in mice. Nature 7286:297–301

    Article  CAS  Google Scholar 

  • Chaudhari N, Landin AM, Roper SD (2000) A metabotropic glutamate receptor variant functions as a taste receptor. Nat Neurosci 3:113–119

    Article  PubMed  CAS  Google Scholar 

  • Chuang CK, Lin SP, Lee HC, Wang TJ, Shih YS, Huang FY, Yeung CY (2005) Free amino acids in full-term and pre-term human milk and infant formula. J Pediatr Gastroenterol Nutr 40:496–500

    Article  PubMed  CAS  Google Scholar 

  • Clapp TR, Yang R, Stoick CL, Kinnamon SC, Kinnamon JC (2004) Morphologic characterization of rat taste receptor cells that express components of the phospholipase C signaling pathway. J Comp Neurol 3:311–321

    Article  CAS  Google Scholar 

  • Clarke GD, Davison JS (1978) Mucosal receptors in the gastric antrum and small intestine of the rat with afferent fibers in the cervical vagus. J Physiol 284:55–67

    PubMed  CAS  Google Scholar 

  • Conigrave AD, Brown EM (2006) Taste receptors in the gastrointestinal tract. II. L-amino acid sensing by calcium-sensing receptors: implications for GI physiology. Am J Physiol Gastrointest Liver Physiol 291:G753–G761

    Article  PubMed  CAS  Google Scholar 

  • Conigrave AD, Quinn SJ, Brown EM (2000) L-amino acid sensing by the extracellular Ca2+-sensing receptor. Proc Natl Acad Sci USA 9:4814–4819

    Article  Google Scholar 

  • Conigrave AD, Mun HC, Lok HC (2007) Aromatic l-amino acids activate the calcium-sensing receptor. J Nutr 6(Suppl 1):1524S–1527S

    Google Scholar 

  • Cordoba JJ, Antequera Rojas T, Garcia Gonzalez C, Ventanas Barroso J, Bote Lopez CJ, Asensio M (1994) Evolution of free amino acids and amines during ripening of iberian cured ham. J Agric Food Chem 42:2296–2301

    Article  CAS  Google Scholar 

  • Curtis RI (2009) Umami and the foods of classical antiquity. Am J Clin Nutr 90:712S–718S

    Article  PubMed  CAS  Google Scholar 

  • Deems DA, Doty RL, Settle RG, Moore-Gillon V, Shaman P, Mester AF, Kimmelman CP, Brightman VJ, Snow JB Jr (1991) Smell and taste disorders, a study of 750 patients form the university of Pennsylvania smell and taste center. Arch Otolaryngol Head Neck Surg 117:519–528

    Article  PubMed  CAS  Google Scholar 

  • DeFazio RA, Dvoryanchikov G, Maruyama Y, Kim JW, Pereira E, Roper SD, Chaudhari N (2006) Separate populations of receptor cells and presynaptic cells in mouse taste buds. J Neurosci 2006(15):3971–3980

    Article  CAS  Google Scholar 

  • DelValle J, Yamada T (1990) Amino acid and amines stimulate gastrin release from canine antral G-cells via different pathways. J Clin Invet 85:139–143

    Article  CAS  Google Scholar 

  • Drake SL, Carunchia Whetstine ME, Drake MA, Courtney P, Fligner K, Jenkins J, Pruitt C (2007) Sources of umami taste in Cheddar and Swiss cheeses. J Food Sci 72:S360–S366

    Article  PubMed  CAS  Google Scholar 

  • Easwood C, Maubach K, Kirkup AJ, Grundy D (1998) The role of endogenous cholecystokinin in the sensory transduction of luminal nutrient signals in the rat jejunum. Neurosci Lett 254:145–148

    Article  Google Scholar 

  • Feng J, Petersen CD, Coy DH, Jiang JK, Thomas CJ, Pollak MR, Wank SA (2010) Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion. Proc Natl Acad Schi USA 107:17791–17796

    Article  CAS  Google Scholar 

  • Fujita T, Kobayashi S, Yui R (1980) Paraneuron concept and its current implications. Adv Biochem Psychoparmacol 25:321–325

    CAS  Google Scholar 

  • Fuke S, Konosu S (1991) Taste-active components in some foods: a review of Japanese research. Physiol Behav 5:863–868

    Article  Google Scholar 

  • Geibel JP, Hebert SC (2009) The functions and roles of the extracellular Ca2+-sensing receptor along the gastrointestinal tract. Annu Rev Physiol 71:205–217

    Article  PubMed  CAS  Google Scholar 

  • Ghosh S, Smriga M, Vuvor F, Suri D, Mohammed H, Armah SM, Scrimshaw NS (2010) Effect of lysine supplementation on health and mobidity in subjects belonging to poor-peri-urban households in Accra, Ghana. Am J Clin Nutr 92:928–939

    Article  PubMed  CAS  Google Scholar 

  • Giduck SA, Threatte RM, Kare MR (1987) Cephalic reflexes: their role in digestion and possible roles in absorption and metabolism. J Nutr 117:1191–1196

    PubMed  CAS  Google Scholar 

  • Goo T, Akiba Y, Kaunitz JD (2010) Mechanisms of intragastric pH sensing. Curr Gastroenterol Rep 12:465–470

    Article  PubMed  Google Scholar 

  • Graham CS, Gaham BG, Bartlett JA, Heald AE, Schiffman SS (1995) Taste and smell losses in HIV infected patients. Physiol Behav 58:287–293

    Article  PubMed  CAS  Google Scholar 

  • Haid D, Widmayer P, Breer H (2011) Nutrient sensing receptors in gastric endocrine cells. J Mol Histol 42:355–364

    Article  PubMed  CAS  Google Scholar 

  • Haid DC, Jordan-Biegger C, Widmayer P, Breer H (2012) Receptors responsive to protein breakdown products in G-cells and D-cells of mouse, swine and human. Front Physiol 3:65

    Article  PubMed  CAS  Google Scholar 

  • Hodson NA, Linden RW (2006) The effect of monosodium glutamate on parotid salivary flow in comparison to the response to representatives of other four basic tastes. Physiol Behav 89:711–717

    Article  PubMed  CAS  Google Scholar 

  • Hofer D, Puschel B, Drenckahn D (1996) Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proc Natl Acad Sci USA 93:6631–6634

    Article  PubMed  CAS  Google Scholar 

  • Hofer D, Asan E, Drenchkhaln D (1999) Chemosensory perception in the gut. News physiol Sci 14:18–23

    PubMed  CAS  Google Scholar 

  • Humayun MA, Elango R, Ball RO, Pencharz PB (2007) Reevaluation of the protein requirement in young indicator amino acid oxidation technique. Am J Clin Nutr 86:995–1002

    PubMed  CAS  Google Scholar 

  • Hundal HS, Taylor PM (2009) Amino acid transceptors: gate keeper of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab 296:E603–E613

    Article  PubMed  CAS  Google Scholar 

  • Iggo A (1957) Gastric mucosal chemoreceptors with vagal afferent fibers in the cat. Q J Exp Physiol Cogn Med Sci 42:398–409

    PubMed  CAS  Google Scholar 

  • Ikeda K (2002) New seasonings. Chem Senses 27:847–849

    Article  PubMed  Google Scholar 

  • Institute of Medicine (US) Committee on Strategies to Reduce Sodium Intake, Henney JE, Taylor CL, Boon CS (eds) (2010) Strategies to reduce sodium intake in the United States. National Academic Press, Washington, DC

  • Institute of Medicine of the National Academies (IOM) (2002/2005) Dietary reference intakes: energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. The National Academy Press, Washington, DC

  • Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, Matsunami H (2006) Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci USA 33:12569–12574

    Article  CAS  Google Scholar 

  • Jahan-Mihan A, Luhovyy BL, El Khoury D, Anderson GH (2011) Dietary proteins as determinants of metabolic and physiologic functions of the gastrointestinal tract. Nutrients 3:574–603

    Article  PubMed  CAS  Google Scholar 

  • Jiang P, Josue J, Li X, Glaser D, Li W, Brand JG, Margolskee RF, Reed DR, Beauchamp GK (2012) Major taste loss in carnivorous mammals. Proc Nalt Acad Sci USA 109:4956–4961

    Article  CAS  Google Scholar 

  • Jin K, Xue C, Wu X, Qian J, Zhu Y, Yang Z, Yonezawa T, Crabbe MJ, Cao Y, Hasegawa M, Zhong Y, Zheng Y (2011) Why does the giant panda eat bamboo? A comparative analysis of appetite-reward-related genes among mammals. PLoS One 7:e22602

    Article  CAS  Google Scholar 

  • Kato H, Rhue ME, Nishimura T (1989) Role of free amino acids and peptides in food taste. In: Teranishi R, Buttery R, Shahidi F (eds) Flavor chemistry, trends and developments. vol 388. ACS, Washington

  • Kawai M, Skine-Hayakawa Y, Okiyama A, Ninomiya Y (2012) Gustatory sensation of L- and D-amino acids in humans. Amino acids. doi:10.1007/s00726-012-1315-x

  • Khropycheva R, Andreeva J, Uneyama H, Torii K, Zolotarev V (2011) Dietary glutmate signal evokes gastric juice excretion in dogs. Digestion 83(Suppl 1):7–12

    Article  PubMed  CAS  Google Scholar 

  • Kinnamon JC, Henzler DM, Royer SM (1993) HVEM ultrastructural analysis of mouse fungiform taste buds, cell types, and associated synapses. Microc Res Tech 26:142–156

    Article  CAS  Google Scholar 

  • Kirchhoff P, Dave MH, Remy C, Kosiek O, Busque SM, Dufner M, Geibel JP, Verrey F, Wagner CA (2006) An amino acid transporter involved in gastric acid secretion. Pflugers Arch 451:738–748

    Article  PubMed  CAS  Google Scholar 

  • Kitamura A, Torii K, Uneyama H, Niijima A (2010) Role played by afferent signals from olfactory, gustatory and gastrointestinal sensors in regulation of autonomic nerve activity. Biol Pharm Bull 33:1778–17782

    Article  PubMed  CAS  Google Scholar 

  • Kitamura A, Sato W, Uneyama H, Torii K, Niijima A (2011) Effects of intragastric infusion of inosine monophosphate and l-glutamate on vagal gastric afferent activity and subsequent autonomic reflexes. J Physiol Sci 61:65–71

    Article  PubMed  CAS  Google Scholar 

  • Konturek SJ, Brzozowski T, Konturek PC, Schubert ML, Pawlik WW, Padol S, Bayner J (2008) Brain–gut and appetite regulating hormones in the control of gastric secretion and mucosal protection. J Physiol Pharmacol 59(Suppl 2):7–31

    PubMed  Google Scholar 

  • Koutsidis G, Elmore JS, Oruna-Concha MJ, Campo MM, Wood JD, Moltram DS (2008) Water-soluble precursors of beef flavor: I. Effect of diet and breed. Meat Sci 79:124–130

    Article  PubMed  CAS  Google Scholar 

  • Kuang D, Yao Y, Kam J, Tsushima RG, Hampson DR (2005) Clonning and characterization of a family C orphan G-protein coupled receptor. J Neurochem 93:383–391

    Article  PubMed  CAS  Google Scholar 

  • Kubo Y, Miyashita T, Murata Y (1998) Structural basesis for a Ca2+-sensing function of the metabotropic glutamate receptors. Science 279:1722–1725

    Article  PubMed  CAS  Google Scholar 

  • Laska M (2010) Olfactory perception of 6 amino acids by human subjects. Chem Senses 35:279–287

    Article  PubMed  CAS  Google Scholar 

  • Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E (2002) Human receptors for sweet and umami taste. Proc Natl Acad Sci USA 99:4692–4696

    Google Scholar 

  • Li X, Li W, Wang H, Cao J, Maehashi K, Huang L, Bachmanov AA, Reed DR, Legrand-Defretin V, Beauchamp GK, Brand JG (2005) Pseudogenization of a sweet-receptor gene accounts for cats’ indifference towards sugar. PLoS Genet 1:27–35

    Article  PubMed  CAS  Google Scholar 

  • Lindemann B (1996) Taste Reception. Physiol Rev 76:719–766

    CAS  Google Scholar 

  • Liou AP, Sei Y, Zhao X, Feng J, Lu X, Thomas C, Pechhold S, Raybould HE, Wank SA (2011) The extracellular calcium-sensing receptor is required for the cholecystokinin secretion in response to l-phenylalanine in acutely isolated intestinal cells. Am J Physiol Gastrointest Liver Physiol 300:G538–G546

    Article  PubMed  CAS  Google Scholar 

  • Martin L, Antequera T, Ventanas J, Benitez-Donoso R, Cordoba JJ (2001) Free amino acids and other non-volatile compounds formed during processing of Iberian ham. Meat Sci 59:363–368

    Article  PubMed  CAS  Google Scholar 

  • Maruyama Y, Yasuda R, Kuroda M, Eto Y (2012) Kokumi substances, enhancers of basic tastes, induce responses in calcium-sensing receptor expressing taste cells. PLoS One 4:e34489

    Article  CAS  Google Scholar 

  • Nakamura E, Hasumura M, San Gabriel A, Uneyama H, Torii K (2010) New frotiers in gut nutrient sensor research: luminal glutamate-sensing cells in rat gastric mucosa. J Pharmacol Sci 112:13–18

    Article  PubMed  CAS  Google Scholar 

  • Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (2001) Mammalian sweet taste receptors. Cell 3:381–390

    Article  Google Scholar 

  • Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS (2002) An amino-acid receptor. Nature 416:199–202

    Article  PubMed  CAS  Google Scholar 

  • Niccolai N, Spadaccini R, Scarselli M, Bernini A, Crescenzi O, Spiga O, Ciutti A, Di Maro D, Bracci L, Davit C, Temussi PA (2001) Probing the surface of a sweet protein: NMR study of MNEI with a paramagnetic probe. Protein Sci 10:1498–1507

    Article  PubMed  CAS  Google Scholar 

  • Niggemann B, Binder C, Dupont C, Hadji S, Arvola T, Isolauri E (2001) Prospective, controlled, multi-center study on the effect of an amino-acid-based formula in infants with cow’s milk allergy/intolerance and atopic dermatitis. Pediatr Allergy Immunol 12:78–82

    Article  PubMed  CAS  Google Scholar 

  • Ninomiya K (1998) Natural occurrence. Food Rev Int 14:177–211

    Article  CAS  Google Scholar 

  • Ninomiya Y, Funakoshi M (1989) Peripheral neural basis for behavioral discrimination between glutamate and the four basic tastes substances in mice. Comp Biochem Physiol A Comp Physiol 92:371–376

    Article  PubMed  CAS  Google Scholar 

  • Ninomiya Y, Tonosaki K, Funakoshi M (1982) Gustatory neural response in the mouse. Brain Res 2:370–373

    Article  Google Scholar 

  • Ninomiya K, Kitamura S, Saiga-Egusa A, Ozawa S, Hirose Y, Kagemori T, Moriki A, Tanaka T, Nishimura T (2010) Changes in free amino acids during heating bouillon prepared at different temperatures. J Home Econ Jpn 61:765–773

    CAS  Google Scholar 

  • Ohsu T, Amino Y, Nagasaki H, Yamanaka T, Takeshita S, Hatanaka T, Maruyama Y, Miyamura N, Eto Y (2010) Involvement of the calcium-sensing receptor in human taste perception. J Biol Chem 2:1016–1022

    Article  CAS  Google Scholar 

  • Oruna-Concha MJ, Methven L, Blumenthal H, Young C, Mottran DS (2007) Differences in glutamic acid and 5′-ribonucleotide contents between flesh and pulp of tomatoes and the relationship with umami taste. J Agric Food Chem 55:5776–5780

    Article  PubMed  CAS  Google Scholar 

  • Pepino Y, Finkbeiner S, Beauchamp G, Mennella J (2010) Obese women have lower monosodium glutamate taste sensitivity and prefer higher concentrations than do normal-weight women. Obesity 18:959–965

    Article  PubMed  Google Scholar 

  • Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF (2002) A transient potential channel expressed in taste receptor cells. Nat Neurosci 5:1169–1176

    Article  PubMed  CAS  Google Scholar 

  • Pi M, Quarles LD (2012) Multiligand specificity and wide tissue expression of GPRC6A reveals new endocrine networks. Endocrinology 5:2062–2069

    Article  CAS  Google Scholar 

  • Pi M, Faber P, Ekema G, Jackson PD, Ting A, Wang N, Fontilla-Poole M, Mays RW, Brunden KR, Harrington JJ, Quarles LD (2005) Identification of a novel extracellular cation-sensing G-protein-coupled receptor. J Biol Chem 280:40201–40209

    Article  PubMed  CAS  Google Scholar 

  • Pi M, Parrill AL, Quarles LD (2010) GPRC6A mediates the non-genomic effects of steroids. J Biol Chem 285:39953–39964

    Article  PubMed  CAS  Google Scholar 

  • Power MK, Schulkin J (2008) Anticipatory physiological regulation in feeding biology: cephalic phase responses. Appetite 50:194–206

    Article  PubMed  Google Scholar 

  • Rasoamanana R, Darcel N, Fromentin G, Tome D (2012) Nutrient sensing and signalling by the gut. Proc Nutr Soc. doi:10.1017/S0029665112000110

    PubMed  Google Scholar 

  • Ray JM, Squires PE, Curtis SB, Meloche MR, Buchan AM (1997) Expression of the calcium-sensing receptor on human antral gastrin cells in culture. J Clin Invest 99:2328–2333

    Article  PubMed  CAS  Google Scholar 

  • Reeds P, Garlick P (2003) Protein and amino acid requirement and the composition of complementary foods. J Nutr 133:2953S–2961S

    PubMed  Google Scholar 

  • Richardson CT, Walsh JH, Hicks MI, Fordtran JS (1976) Studies on the mechanisms of food-stimulated gastric acid secretion in normal human subjects. J Clin Invest 58:623–631

    Article  PubMed  CAS  Google Scholar 

  • Roper SD (2007) Signal transduction and information processing in mammalian taste buds. Pflugers Arch 5:759–776

    Article  CAS  Google Scholar 

  • Roura E, Humphrey B, Klasing K, Swart M (2011) Is the pig a good umami sensing model for humans? A comparative taste receptor study. Flavour Frag J 26:282–285

    Article  CAS  Google Scholar 

  • Saffouri B, DuVal JW, Makhlouf GM (1984) Stimulation of gastrin secretion in vitro by intraluminal chemicals: regulation by intramural cholinergic and noncholinergic neurons. Gastroenterology 87:557–561

    PubMed  CAS  Google Scholar 

  • Saidak Z, Brazier M, Kamel S, Mentaverri R (2009) Agonists and allosteric modulators of the calcium-sensing receptor and their therapeutic applications. Mol Pharmacol 6:1131–1144

    Article  CAS  Google Scholar 

  • Sampath-Kumar PS, Fruton JS (1974) Studies on the extend active sites of acid proteases. Proc Natl Acad Sci USA 71:1070–1072

    Article  PubMed  CAS  Google Scholar 

  • San Gabriel AM, Maekawa T, Uneyama H, Yoshie S, Torii K (2007) mGluR1 in the fundic glands of rat stomach. FEBS Lett 581:1119–1123

    Article  PubMed  CAS  Google Scholar 

  • San Gabriel A, Uneyama H, Maekawa T, Torii K (2009a) The calcium-sensing receptor in taste tissue. Biochem Biophys Res Commun 378:414–418

    Article  PubMed  CAS  Google Scholar 

  • San Gabriel A, Maekawa T, Uneyama H, Torii K (2009b) Metabotropic glutamate receptor type 1 in taste tissue. Am J Clin Nutr 3:743S–746S

    Article  CAS  Google Scholar 

  • Sarwar G, Botting HG, Davis TA, Darling P, Pencharz PB (1998) Free amino acids in milk of human subjects, other primates and non-primates. Br J Nutr 79:129–131

    Article  PubMed  CAS  Google Scholar 

  • Sasano T, Satoh-Kuriwada S, Shoji N, Kawai M, Sekine-Hayakawa Y, Uneyama H (2010) Application of umami taste stimulation to remedy hypogeusia based on reflex salivation. Biol Pharm Bull 33:1791–1795

    Article  PubMed  CAS  Google Scholar 

  • Sbarbati A, Osculati F (2005) The taste cell-related diffuse chemosensory system. Prog Neurobiol 75:295–307

    Article  PubMed  CAS  Google Scholar 

  • Schiffman SS, Graham BG (2000) Taste and smell perception affect appetite and immunity in the elderly. Eur J Clin Nutr 54(Suppl3):S54–S63

    Article  PubMed  Google Scholar 

  • Schiffman S, Hornack K, Reilly D (1979) Increased taste thresholds of amino acids with age. Am J Clin Nutr 32:1622–1627

    PubMed  CAS  Google Scholar 

  • Schubert ML, Jong MJ, Makhlouf GM (1991) Bombesin/GRP-stimulated somatostatin secretion is mediated by gastrin in the antrum and intrinsic neurons in the fundus. Am J Physiol 261:G885–G889

    PubMed  CAS  Google Scholar 

  • Shigemura N, Ohkuri T, Sadamitsu C, Yasumatsu K, Yoshida R, Beauchamp GK, Bachmanov AA, Ninomiya Y (2008) Amiloride-sensitive NaCl taste responses are associated with genetic variation of ENaC alpha-subunit in mice. Am J Physiol Regul Integr Comp Physiol 1:R66–R75

    Google Scholar 

  • Shimizu M (2010) Interaction between food substances and the intestinal epithelium. Biosci Biotechnol Biochem 74:232–241

    Article  PubMed  CAS  Google Scholar 

  • Shubert ML (2009) Gastric exocrine and endocrine secretion. Curr Opin Gastroenterol 25:529–536

    Article  CAS  Google Scholar 

  • Silk DB (1980) Digestion and absorption of dietary protein in man. Proc Nutr Soc 39:61–70

    Article  PubMed  CAS  Google Scholar 

  • Sorrequieta A, Ferraro G, Boggio SB, Valle EM (2010) Free amino acid production during tomato fruit ripening: a focus on l-glutamate. Amino acids 38:1523–1532

    Article  PubMed  CAS  Google Scholar 

  • Steinert RE, Beglinger C (2011) Nutrient sensing in the gut: interactions between chemosensory cells, visceral afferents and the secretion of satiation peptides. Physiol Behav 105:62–70

    Article  PubMed  CAS  Google Scholar 

  • Stewart JE, Feinte-Bisset C, Golding M, Delahunty C, Clifton PM, Keast RS (2010) Oral Sensitivity to fatty acids, food consumption and BMI in human subjects. Br J Nutr 104:145–152

    Article  PubMed  CAS  Google Scholar 

  • Strunz UT, Walsh JH, Grossman MI (1978) Stimulation of gastrin release in dogs by individual amino acids. Proc Soc Exp Bio Med 157:440–441

    Article  CAS  Google Scholar 

  • Svanberg U, Gebre-Medhin M, Ljungqvist B, Olsson M (1977) Breast milk composition in Ethiopian and Swedish mothers. III Amino acids and other nitrogenous substances. Am J Clin Nutr 30:499–507

    PubMed  CAS  Google Scholar 

  • Taylor IL, Byrne WJ, Christie DL, Ament ME, Walsh JH (1982) Effect of individual l-amino acids on gastric acid secretion and serum gastrin and pancreatic polypeptide release in humans. Gastroenterology 83(1 Pt 2):273–278

    PubMed  CAS  Google Scholar 

  • Tomoe M, Inoue Y, Sanbe A, Toyama K, Yamamoto S, Komatsu T (2009) Clinical trial of glutamate for the improvement of nutrition and health in the elderly. Ann N Y Acad Sci 1170:82–86

    Article  PubMed  CAS  Google Scholar 

  • Tordoff MG, Shao H, Alarcon LK, Margolskee RF, Mosinger B, Bachmanov AA, Reed DR, McCaughey S (2008) Involvement of T1R3 in calcium–magnesium taste. Physiol Genomics 3:338–348

    Google Scholar 

  • Toyono T, Seta Y, Kataoka S, Kawano S, Shigemoto R, Toyoshima K (2003) Expression of metabotropic glutamate receptor group I in rat gustatory papillae. Cell Tissue Res 2:29–35

    Article  CAS  Google Scholar 

  • Toyono T, Kataoka S, Seta Y, Shigemoto R, Toyoshima K (2007) Expression of group II metabotropic glutamate receptors in rat gustatory papillae. Cell Tissue Res 1:57–63

    Article  CAS  Google Scholar 

  • Ugawa S, Yamamoto T, Ueda T, Ishida Y, Inagaki A, Nishigaki M, Shimada S (2003) Amiloride-insensitive currents of the acid-sensing ion channel-2a (ASIC2a)/ASIC2b heteromeric sour-taste receptor channel. J Nuerosci 9:3616–3622

    Google Scholar 

  • Uneyama H, Nijjima A, San Gabriel A, Torii K (2006) Luminal amino acid sensing in the rat gastric mucosa. Am J Physiol Gastrointest Liver Physiol 6:G1163–G1170

    Article  CAS  Google Scholar 

  • Voynick IM, Fruton JS (1971) The comparative specificity of acid proteases. Proc Natl Acad Sci USA 68:257–259

    Article  PubMed  CAS  Google Scholar 

  • Wang M, Yao Y, Kuang D, Hampson DR (2006) Activation of family C G-protein-coupled receptors by the tripeptide glutathione. J Biol Chem 13:8864–8870

    Article  CAS  Google Scholar 

  • Wellendorph P, Hansen KB, Balsgarrd A, Greenwood JR, Egebjerg J, Brauner-Osborne H (2005) Deorphanization of GPRC6A: a promiscuous L-alpha-amino acid receptor with preference for basic amino acids. Mol Pharmacol 67:589–597

    Article  PubMed  CAS  Google Scholar 

  • Wellendorph P, Burhenne N, Christiansen B, Walter B, Schmale H, Brauner-Osborne H (2007) The rat GPRC6A: cloning and characterization. Gene 396:257–267

    Article  PubMed  CAS  Google Scholar 

  • Wellendorph P, Johansen LD, Brauner-Osborne H (2009) Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients. Mol Pharmacol 3:453–465

    Article  CAS  Google Scholar 

  • Wu G (2010) Functional amino acids in growth, reproduction, and health. Adv Nutr 1:31–37

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Knabe DA (1994) Free and protein-bound amino acids in sow’s colostrum and milk. J Nutr 124:415–424

    Google Scholar 

  • Xu H, Staszewski L, Tang H, Adler E, Zoller M, Li X (2004) Different functional roles of T1R subunits in the heteromeric taste receptors. Proc Natl Acad Sci USA 101:14258–14263

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi S (1998) Basic properties of umami and its effects on food flavors. Food Rev Int 14(2 and 3):139–176

    Google Scholar 

  • Yasumatsu K, Horio N, Murata Y, Shirosaki S, Ohkuri T, Yoshida R, Ninomiya Y (2009) Multiple receptors underlie glutamate taste responses in mice. Am J Clin Nutr 3:747S–752S

    Article  CAS  Google Scholar 

  • Yoshida Y (1998) Umami taste and traditional seasonings. Food Rev Int 14:213–246

    Article  CAS  Google Scholar 

  • Yoshida R, Horio N, Murata Y, Yasumatsu K, Shigemura N, Ninomiya Y (2009a) NaCl responsive taste cells in mouse fungiform taste buds. Neuroscience 2:795–803

    Article  CAS  Google Scholar 

  • Yoshida R, Miyauchi A, Yasuo T, Jyotaki M, Murata Y, Yasumatsu K, Shigemura N, Yanagawa Y, Obata K, Ueno H, Margolskee RF, Ninomiya Y (2009b) Discrimination of taste qualities among mouse fungiform taste buds cells. J Physiol Pt 18:4425–4439

    Article  CAS  Google Scholar 

  • Zhang Y, Hoon MA, Chandrashaker J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ (2003) Coding of sweet, bitter, and umami taste: different receptor cells sharing similar signaling pathways. Cell 112:293–301

    Article  PubMed  CAS  Google Scholar 

  • Zolotarev V, Khropycheva R, Uneyama H, Torii K (2009) Effect of free dietary glutamate on gastric secretion in dogs. Ann N Y Acad Sci 1170:87–90

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

I would like to thank Dr. Eiji Nakamura for his critical comments and discussions during the preparation of this manuscript.

Conflict of interest

Both authors are employees of Ajinomoto Co., Inc.

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Correspondence to Ana San Gabriel.

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San Gabriel, A., Uneyama, H. Amino acid sensing in the gastrointestinal tract. Amino Acids 45, 451–461 (2013). https://doi.org/10.1007/s00726-012-1371-2

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  • DOI: https://doi.org/10.1007/s00726-012-1371-2

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