https://doi.org/10.4081/ejh.2022.3534

Expression profile of the zinc transporter ZnT3 in taste cells of rat circumvallate papillae and its role in zinc release, a potential mechanism for taste stimulation

Vol. 66 No. 4 (2022)
Submitted: 16 August 2022
Accepted: 28 October 2022
Published: 10 November 2022
zinc, zinc transporter, taste cell, taste bud, circumvallate papilla, lingual epithelium, taste signaling
Abstract Views: 739
PDF: 475
Supplementary: 82
HTML: 27
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Kentaro Nishida
nishidak.c6@gmail.com
https://orcid.org/0000-0001-8597-4848
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Kyoto; Department of Integrative Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Saho Bansho
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Kyoto , Japan.
Akiko Ikukawa
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Kyoto , Japan.
Teruyo Kubota
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Kyoto , Japan.
Akihiro Ohishi
https://orcid.org/0000-0003-2756-1177
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Kyoto , Japan.
Kazuki Nagasawa
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Kyoto , Japan.

Zinc is an essential trace element, and its deficiency causes taste dysfunction. Zinc accumulates in zinc transporter (ZnT)3-expressing presynaptic vesicles in hippocampal neurons and acts as a neurotransmitter in the central nervous system. However, the distribution of zinc and its role as a signal transmitter in taste buds remain unknown. Therefore, we examined the distribution of zinc and expression profiles of ZnT3 in taste cells and evaluated zinc release from isolated taste cells upon taste stimuli. Taste cells with a spindle or pyriform morphology were revealed by staining with the fluorescent zinc dye ZnAF-2DA and autometallography in the taste buds of rat circumvallate papillae. Znt3 mRNA levels were detected in isolated taste buds. ZnT3-immunoreactivity was found in phospholipase-β2-immunopositive type II taste cells and aromatic amino acid decarboxylase-immunopositive type III cells but not in nucleoside triphosphate diphosphohydrolase 2-immunopositive type I cells. Moreover, we examined zinc release from taste cells using human transient receptor potential A1-overexpressing HEK293 as zinc-sensor cells. These cells exhibited a clear response to isolated taste cells exposed to taste stimuli. However, pretreatment with magnesium-ethylenediaminetetraacetic acid, an extracellular zinc chelator - but not with zinc-ethylenediaminetetraacetic acid, used as a negative control - significantly decreased the response ratio of zinc-sensor cells. These findings suggest that taste cells release zinc to the intercellular area in response to taste stimuli and that zinc may affect signaling within taste buds.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
Atkin-Thor E, Goddard BW, O'Nion J, Stephen RL, Kolff WJ. Hypogeusia and zinc depletion in chronic dialysis patients. Am J Clin Nutr 1978;31:1948-51. DOI: https://doi.org/10.1093/ajcn/31.10.1948
Heyneman CA. Zinc deficiency and taste disorders. Ann Pharmacother 1996;30:186-7. DOI: https://doi.org/10.1177/106002809603000215
Mahajan SK, Prasad AS, Lambujon J, Abbasi AA, Briggs WA, McDonald FD. Improvement of uremic hypogeusia by zinc: a double-blind study. Am J Clin Nutr 1980;33:1517-21. DOI: https://doi.org/10.1093/ajcn/33.7.1517
Weismann K, Christensen E, Dreyer V. Zinc supplementation in alcoholic cirrhosis. A double-blind clinical trial. Acta Med Scand 1979;205:361-6. DOI: https://doi.org/10.1111/j.0954-6820.1979.tb06065.x
Hewlings S, Kalman D. A Review of zinc-l-carnosine and its positive effects on oral mucositis, taste disorders, and gastrointestinal disorders. Nutrients 2020;12:665. DOI: https://doi.org/10.3390/nu12030665
Chou HC, Chien CL, Huang HL, Lu KS. Effects of zinc deficiency on the vallate papillae and taste buds in rats. J Formos Med Assoc 2001;100:326-35.
Hamano H, Yoshinaga K, Eta R, Emori Y, Kawasaki D, Iino Y, et al. Effect of polaprezinc on taste disorders in zinc-deficient rats. Biofactors 2006;28:185-93. DOI: https://doi.org/10.1002/biof.5520280305
Jakinovich W, Jr., Osborn DW. Zinc nutrition and salt preference in rats. Am J Physiol 1981;241:R233-9. DOI: https://doi.org/10.1152/ajpregu.1981.241.3.R233
Perez-Clausell J, Danscher G. Intravesicular localization of zinc in rat telencephalic boutons. A histochemical study. Brain Res 1985;337:91-8. DOI: https://doi.org/10.1016/0006-8993(85)91612-9
Frederickson CJ, Moncrieff DW. Zinc-containing neurons. Biol Signals 1994;3:127-39. DOI: https://doi.org/10.1159/000109536
Haug FM. Electron microscopical localization of the zinc in hippocampal mossy fibre synapses by a modified sulfide silver procedure. Histochemie 1967;8:355-68. DOI: https://doi.org/10.1007/BF00401978
Ma B, Ruan HZ, Burnstock G, Dunn PM. Differential expression of P2X receptors on neurons from different parasympathetic ganglia. Neuropharmacology 2005;48:766-77. DOI: https://doi.org/10.1016/j.neuropharm.2004.12.021
Takeda A, Sakurada N, Ando M, Kanno S, Oku N. Facilitation of zinc influx via AMPA/kainate receptor activation in the hippocampus. Neurochem In. 2009;55:376-82. DOI: https://doi.org/10.1016/j.neuint.2009.04.006
Amico-Ruvio SA, Murthy SE, Smith TP, Popescu GK. Zinc effects on NMDA receptor gating kinetics. Biophys J 2011;100:1910-8. DOI: https://doi.org/10.1016/j.bpj.2011.02.042
Qian J, Noebels JL. Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapse. J Physiol 2005;566:747-58. DOI: https://doi.org/10.1113/jphysiol.2005.089276
Westbrook GL, Mayer ML. Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons. Nature 1987;328:640-3. DOI: https://doi.org/10.1038/328640a0
Farbman AI. Fine structure of the taste bud. J Ultrastruct Res 1965;12:328-50. DOI: https://doi.org/10.1016/S0022-5320(65)80103-4
Takeda M, Hoshino T. Fine structure of taste buds in the rat. Arch Histol Jpn 1975;37:395-413. DOI: https://doi.org/10.1679/aohc1950.37.395
Yang R, Dzowo YK, Wilson CE, Russell RL, Kidd GJ, Salcedo E, et al. Three-dimensional reconstructions of mouse circumvallate taste buds using serial blockface scanning electron microscopy: I. Cell types and the apical region of the taste bud. J Comp Neurol 2020;528:756-71. DOI: https://doi.org/10.1002/cne.24779
Bartel DL, Sullivan SL, Lavoie EG, Sevigny J, Finger TE. Nucleoside triphosphate diphosphohydrolase-2 is the ecto-ATPase of type I cells in taste buds. J Comp Neurol 2006;497:1-12. DOI: https://doi.org/10.1002/cne.20954
Dvoryanchikov G, Sinclair MS, Perea-Martinez I, Wang T, Chaudhari N. Inward rectifier channel, ROMK, is localized to the apical tips of glial-like cells in mouse taste buds. J Comp Neurol 2009;517:1-14. DOI: https://doi.org/10.1002/cne.22152
Lawton DM, Furness DN, Lindemann B, Hackney CM. Localization of the glutamate-aspartate transporter, GLAST, in rat taste buds. Eur J Neurosci 2000;12:3163-71. DOI: https://doi.org/10.1046/j.1460-9568.2000.00207.x
Chaudhari N, Roper SD. The cell biology of taste. J Cell Biol 2010;190:285-96. DOI: https://doi.org/10.1083/jcb.201003144
Finger TE, Danilova V, Barrows J, Bartel DL, Vigers AJ, Stone L, et al. ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 2005;310:1495-9. DOI: https://doi.org/10.1126/science.1118435
Romanov RA, Rogachevskaja OA, Bystrova MF, Jiang P, Margolskee RF, Kolesnikov SS. Afferent neurotransmission mediated by hemichannels in mammalian taste cells. EMBO J 2007;26:657-67. DOI: https://doi.org/10.1038/sj.emboj.7601526
Huang YJ, Maruyama Y, Lu KS, Pereira E, Plonsky I, Baur JE, et al. Mouse taste buds use serotonin as a neurotransmitter. J Neurosci 2005;25:843-7. DOI: https://doi.org/10.1523/JNEUROSCI.4446-04.2005
Vandenbeuch A, Zorec R, Kinnamon SC. Capacitance measurements of regulated exocytosis in mouse taste cells. J Neurosci 2010;30:14695-701. DOI: https://doi.org/10.1523/JNEUROSCI.1570-10.2010
Herness S, Zhao FL, Kaya N, Lu SG, Shen T, Sun XD. Adrenergic signalling between rat taste receptor cells. J Physiol 2002;543:601-14. DOI: https://doi.org/10.1113/jphysiol.2002.020438
Dvoryanchikov G, Huang YA, Barro-Soria R, Chaudhari N, Roper SD. GABA, its receptors, and GABAergic inhibition in mouse taste buds. J Neurosci 2011;31:5782-91. DOI: https://doi.org/10.1523/JNEUROSCI.5559-10.2011
Ogura T. Acetylcholine increases intracellular Ca2+ in taste cells via activation of muscarinic receptors. J Neurophysiol 2002;87:2643-9. DOI: https://doi.org/10.1152/jn.2002.87.6.2643
Taruno A, Vingtdeux V, Ohmoto M, Ma Z, Dvoryanchikov G, Li A, et al. CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 2013;495:223-6. DOI: https://doi.org/10.1038/nature11906
DeFazio RA, Dvoryanchikov G, Maruyama Y, Kim JW, Pereira E, Roper SD, et al. Separate populations of receptor cells and presynaptic cells in mouse taste buds. J Neurosci 2006;26:3971-80. DOI: https://doi.org/10.1523/JNEUROSCI.0515-06.2006
Huang YA, Dando R, Roper SD. Autocrine and paracrine roles for ATP and serotonin in mouse taste buds. J Neurosci 2009;29:13909-18. DOI: https://doi.org/10.1523/JNEUROSCI.2351-09.2009
Yang R, Tabata S, Crowley HH, Margolskee RF, Kinnamon JC. Ultrastructural localization of gustducin immunoreactivity in microvilli of type II taste cells in the rat. J Comp Neurol 2000;425:139-51. DOI: https://doi.org/10.1002/1096-9861(20000911)425:1<139::AID-CNE12>3.0.CO;2-#
Liman ER, Kinnamon SC. Sour taste: receptors, cells and circuits. Curr Opin Physiol 2021;20:8-15. DOI: https://doi.org/10.1016/j.cophys.2020.12.006
Tu YH, Cooper AJ, Teng B, Chang RB, Artiga DJ, Turner HN, et al. An evolutionarily conserved gene family encodes proton-selective ion channels. Science 2018;359:1047-50. DOI: https://doi.org/10.1126/science.aao3264
Zhang J, Jin H, Zhang W, Ding C, O'Keeffe S, Ye M, et al. Sour sensing from the tongue to the brain. Cell 2019;179:392-402.e15. DOI: https://doi.org/10.1016/j.cell.2019.08.031
Teng B, Wilson CE, Tu YH, Joshi NR, Kinnamon SC, Liman ER. Cellular and neural responses to sour stimuli require the proton channel otop1. Curr Biol 2019;29:3647-56.e5. DOI: https://doi.org/10.1016/j.cub.2019.08.077
Kinnamon JC, Taylor BJ, Delay RJ, Roper SD. Ultrastructure of mouse vallate taste buds. I. Taste cells and their associated synapses. J Comp Neurol 1985;235:48-60. DOI: https://doi.org/10.1002/cne.902350105
Fujimoto S, Ueda H, Kagawa H. Immunocytochemistry on the localization of 5-hydroxytryptamine in monkey and rabbit taste buds. Acta Anat (Basel) 1987;128:80-3. DOI: https://doi.org/10.1159/000146320
Yee CL, Yang R, Bottger B, Finger TE, Kinnamon JC. "Type III" cells of rat taste buds: immunohistochemical and ultrastructural studies of neuron-specific enolase, protein gene product 9.5, and serotonin. J Comp Neurol 2001;440:97-108. DOI: https://doi.org/10.1002/cne.1372
Dvoryanchikov G, Tomchik SM, Chaudhari N. Biogenic amine synthesis and uptake in rodent taste buds. J Comp Neurol 2007;505:302-13. DOI: https://doi.org/10.1002/cne.21494
Nishida K, Dohi Y, Yamanaka Y, Miyata A, Tsukamoto K, Yabu M, et al. Expression of adenosine A2b receptor in rat type II and III taste cells. Histochem Cell Biol 2014;141:499-506. DOI: https://doi.org/10.1007/s00418-013-1171-0
Danscher G, Haug FM, Fredens K. Effect of diethyldithiocarbamate (DEDTC) on sulphide silver stained boutons. Reversible blocking of Timm's sulphide silver stain for "heavy" metals in DEDTC treated rats (light microscopy). Exp Brain Res 1973;16:521-32. DOI: https://doi.org/10.1007/BF00234478
Danscher G. Histochemical demonstration of heavy metals. A revised version of the sulphide silver method suitable for both light and electronmicroscopy. Histochemistry 1981;71:1-16. DOI: https://doi.org/10.1007/BF00592566
Danscher G, Stoltenberg M. Zinc-specific autometallographic in vivo selenium methods: tracing of zinc-enriched (ZEN) terminals, ZEN pathways, and pools of zinc ions in a multitude of other ZEN cells. J Histochem Cytochem 2005;53:141-53. DOI: https://doi.org/10.1369/jhc.4R6460.2005
Hu H, Bandell M, Petrus MJ, Zhu MX, Patapoutian A. Zinc activates damage-sensing TRPA1 ion channels. Nat Chem Biol 2009;5:183-90. DOI: https://doi.org/10.1038/nchembio.146
Ohmoto M, Matsumoto I, Misaka T, Abe K. Taste receptor cells express voltage-dependent potassium channels in a cell age-specific manner. Chem Senses 2006;31:739-46. DOI: https://doi.org/10.1093/chemse/bjl016
Clapp TR, Yang R, Stoick CL, Kinnamon SC, Kinnamon JC. Morphologic characterization of rat taste receptor cells that express components of the phospholipase C signaling pathway. J Comp Neurol 2004;468:311-21. DOI: https://doi.org/10.1002/cne.10963
Seta Y, Kataoka S, Toyono T, Toyoshima K. Immunohistochemical localization of aromatic L-amino acid decarboxylase in mouse taste buds and developing taste papillae. Histochem Cell Biol 2007;127:415-22. DOI: https://doi.org/10.1007/s00418-006-0257-3
Besser L, Chorin E, Sekler I, Silverman WF, Atkin S, Russell JT, et al. Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus. J Neurosci 2009;29:2890-901. DOI: https://doi.org/10.1523/JNEUROSCI.5093-08.2009
Huang YJ, Maruyama Y, Dvoryanchikov G, Pereira E, Chaudhari N, Roper SD. The role of pannexin 1 hemichannels in ATP release and cell-cell communication in mouse taste buds. Proc Natl Acad Sci USA 2007;104:6436-41. DOI: https://doi.org/10.1073/pnas.0611280104
Huang YA, Roper SD. Intracellular Ca(2+) and TRPM5-mediated membrane depolarization produce ATP secretion from taste receptor cells. J Physiol 2010;588:2343-50. DOI: https://doi.org/10.1113/jphysiol.2010.191106
Murata Y, Yasuo T, Yoshida R, Obata K, Yanagawa Y, Margolskee RF, et al. Action potential-enhanced ATP release from taste cells through hemichannels. J Neurophysiol 2010;104:896-901. DOI: https://doi.org/10.1152/jn.00414.2010
Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, et al. A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 2002;5:1169-76. DOI: https://doi.org/10.1038/nn952
Liu D, Liman ER. Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci USA 2003;100:15160-5. DOI: https://doi.org/10.1073/pnas.2334159100
Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, et al. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 2003;112:293-301. DOI: https://doi.org/10.1016/S0092-8674(03)00071-0
Zhang Z, Zhao Z, Margolskee R, Liman E. The transduction channel TRPM5 is gated by intracellular calcium in taste cells. J Neurosci 2007;27:5777-86. DOI: https://doi.org/10.1523/JNEUROSCI.4973-06.2007
Uchida K, Tominaga M. Extracellular zinc ion regulates transient receptor potential melastatin 5 (TRPM5) channel activation through its interaction with a pore loop domain. J Biol Chem 2013;288:25950-5. DOI: https://doi.org/10.1074/jbc.M113.470138
Wildman SS, King BF, Burnstock G. Zn2+ modulation of ATP-responses at recombinant P2X2 receptors and its dependence on extracellular pH. Br J Pharmacol 1998;123:1214-20. DOI: https://doi.org/10.1038/sj.bjp.0701717
Xiong K, Peoples RW, Montgomery JP, Chiang Y, Stewart RR, Weight FF, et al. Differential modulation by copper and zinc of P2X2 and P2X4 receptor function. J Neurophysiol 1999;81:2088-94. DOI: https://doi.org/10.1152/jn.1999.81.5.2088

How to Cite

Nishida, K., Bansho, S. ., Ikukawa, A. ., Kubota, T. ., Ohishi, A. ., & Nagasawa, . K. . (2022). Expression profile of the zinc transporter ZnT3 in taste cells of rat circumvallate papillae and its role in zinc release, a potential mechanism for taste stimulation. European Journal of Histochemistry, 66(4). https://doi.org/10.4081/ejh.2022.3534
Copyright (c) 2022 The Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.