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Research in polymorphisms in human taste receptor genes and taste disorder

Research Project

Project/Area Number 14370549
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionNagoya City University

Principal Investigator

SHIMADA Shoichi  Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学兼研究科, 教授 (20216063)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Shingo  Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学兼研究科, 教授 (80157750)
UGAWA Shinya  Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学兼研究科, 講師 (20326135)
植田 高史  名古屋市立大学, 大学院・医学研究科, 助手 (90244540)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
Keywordstaste receptor / hT2R / G protein / bitter taste receptor / calcium imaging / hT2R16 / gustducin / salicin / G蛋白
Research Abstract

T2Rs comprise a G-protein-coupled receptor superfamily that contains functionally defined bitter taste receptors. We found coding single-nucleotide polymorphisms (cSNPs) in human T2R genes (hT2R3, hT2R4, and hT2R5) on chromosome 7q31. We identified six cSNPs within the T2R receptor genes. The hT2R4 and hT2R5 contained four and on cSNPs that cause missense mutations, respectively, while hT2R3 included one silent nucleotide mutation. However, we could not find any nonsense mutations that resulted in a frameshift or a premature stop codon within the open reading frames. T2R receptors and a G-protein α subunit (Gα), gustducin, are believed to be key molecules for its perception, but little is known about the molecular basis for its interaction. We use a heterologous expression system to determine a specific domain of gustducin necessary for T2R coupling. Two chimeric Gα16 proteins harboring 37 and 44 gustducin-specific sequences at their C termini (G16/gust37 and G16/gust44) responded to different T2R receptors with known ligands, but G16/gust23, G16/gust11, and G16/gust5 did not. The former two chimeras contained a predicted β6 sheet, an α5 helix, and an extreme C terminus of gustducin, and all the domains were indispensable to the expression of T2R activity. We also expressed G16 protein chimeras with the corresponding domain from other Gαi proteins, cone-transducin (Gαt2), Gαi2, and Gαz (G16/t2, G16/i2, and G16/z). As a result, G16/t2 and G16/i2 produced specific responses of T2Rs, but G16/z did not. Using Gα16-based chimeras and hT2R16 variants, we examined sensitivity to salicin. Identification of nucleotide diversity and amino acid polymorphisms in human T2R receptors could help clarify individual differences in the acceptability and sensitivity to bitter compounds.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (36 results)

All 2005 2004 2003 2002 Other

All Journal Article (26 results) Book (1 results) Publications (9 results)

  • [Journal Article] Icilin activates the delta-subunit of the human epithelial Na+ channel.2005

    • Author(s)
      Yamamura H., et al.
    • Journal Title

      Molecular Pharmacology 68

      Pages: 1142-1147

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 14-3-3 proteins modulate the expression of epithelial Na+ channels by phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase.2005

    • Author(s)
      Ichimura T., et al.
    • Journal Title

      Journal of Biological Chemistry 280

      Pages: 13187-13194

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Evans blue is a specific antagonist of the human epithelial Na+ channel delta-subunit.2005

    • Author(s)
      Yamamura H., et al.
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics 315

      Pages: 965-969

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] In situ hybridization evidence for the coexistence of ASIC and TRPV1 within rat single sensory neurons.2005

    • Author(s)
      Ugawa S., et al.
    • Journal Title

      Molecular Brain Research 136

      Pages: 125-133

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Effect of benzalkonium chloride on transscleral drug delivery.2005

    • Author(s)
      Okabe K., et al.
    • Journal Title

      Investigative Ophthalmology & Visual Science 46

      Pages: 703-708

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Histopathologic evaluation of the internal limiting membrane surgically excised from eyes with diabetic maculopathy.2005

    • Author(s)
      Matsunaga N., et al.
    • Journal Title

      Retina 25

      Pages: 311-316

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Icilin activates the delta-subunit of the human epithelial Na+ channel.2005

    • Author(s)
      Yamamura H, et al.
    • Journal Title

      Mol Pharmacol. 68

      Pages: 1142-1147

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 14-3-3 proteins modulate the expression of epithelial Na+ channels by phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase.2005

    • Author(s)
      Ichimura T, et al.
    • Journal Title

      J Biol Chem. 280

      Pages: 13187-13194

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Evans blue is a specific antagonist of the human epithelial Na+ channel delta-subunit.2005

    • Author(s)
      Yamamura H, et al.
    • Journal Title

      J Pharmacol Exp Ther. 315

      Pages: 965-969

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In situ hybridization evidence for the coexistence of ASIC and TRPV1 within rat single sensory neurons.2005

    • Author(s)
      Ugawa S, et al.
    • Journal Title

      Mol Brain Res. 136

      Pages: 125-133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of benzalkonium chloride on transscleral drug delivery.2005

    • Author(s)
      Okabe K, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci. 46

      Pages: 703-708

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histopathologic evaluation of the internal limiting membrane surgically excised from eyes with diabetic maculopathy.2005

    • Author(s)
      Matsunaga N, et al.
    • Journal Title

      Retina 25

      Pages: 311-316

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Capsazepine is a novel activator of the delta subunit of the human epithelial Na+ channel2004

    • Author(s)
      Yamamura H., et al.
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 4483-4489

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protons activate the delta-subunit of the epithelial Na+ channel in humans.2004

    • Author(s)
      Yamamura H., et al.
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 12529-12534

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Capsazepine Is a Novel Activator of the{delta}Subunit of the Human Epithelial Na+ Channel.2004

    • Author(s)
      Yamamura H, et al.
    • Journal Title

      J Biol Chem. 279

      Pages: 44483-44489

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protons activate the delta-subunit of the epithelial Na^+ channel in humans.2004

    • Author(s)
      Yamamura H, et al.
    • Journal Title

      J Biol Chem. 279

      Pages: 12529-12534

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Capsazepine is a novel activator of the delta subunit of the human epithelial Na+ channel.2004

    • Author(s)
      Yamamura H., et al.
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 4483-4489

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Functional analysis of acid sensing ion channels2004

    • Author(s)
      Shimada S., et al.
    • Journal Title

      Japanese Journal of Neuropsychopharmacology 24

      Pages: 243-246

    • NAID

      10015423464

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Functional interaction between T2R taste receptors and G-protein alpha subunits expressed in taste receptor cells.2003

    • Author(s)
      Ueda T., et al.
    • Journal Title

      Journal of Neuroscience 23

      Pages: 7376-7380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amiloride-insensitive currents of the ASIC2a/ASIC2b heteroineric sour-taste receptor channel.2003

    • Author(s)
      Ugawa S., et al.
    • Journal Title

      Journal of Neuroscience 23

      Pages: 3616-3622

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functional interaction between T2R taste receptors and G-protein alpha subunits expressed in taste receptor cells.2003

    • Author(s)
      Ueda T, et al.
    • Journal Title

      J Neurosci, 23

      Pages: 7376-7380

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amiloride-insensitive currents of the ASIC2a/ASIC2b heteromeric sour-taste receptor channel.2003

    • Author(s)
      Ugawa S, et al.
    • Journal Title

      J Neurosci, 23

      Pages: 3616-3622

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors.2002

    • Author(s)
      Ugawa S., et al.
    • Journal Title

      Journal of Clinical Investigation 110

      Pages: 1185-1190

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vanilloid receptor subtype-1 (VR1) is specifically localized to taste papillae.2002

    • Author(s)
      Ishida Y., et al.
    • Journal Title

      Molecular Brain Research 107

      Pages: 17-22

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors.2002

    • Author(s)
      Ugawa S, et al.
    • Journal Title

      J Clin Invest. 110

      Pages: 1185-1190

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vanilloid receptor subtype-1(VR1) is specifically localized to taste papillae.2002

    • Author(s)
      Ishida Y, et al.
    • Journal Title

      Mol Brain Res. 107

      Pages: 17-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] イオンチャネル最前線update2005

    • Author(s)
      島田昌一
    • Publisher
      医歯薬出版株式会社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Publications] UedaT., et al.: "Functional interaction between T2R taste receptors and G-protein alpha subunit expressed in taste receptor cells"Journal of Neuroscience. 23. 7376-7380 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ugawa S., et al.: "Amiloride-insensitive currents of the ASIC2a/ASIC2b heteromeric sour-taste receptor channel"Journal of Neuroscience. 23. 3616-3622 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamamura H., et al.: "Protons activate the δ-subunit of the epithelial Na channel in humans"Journal of Biological Chemistry. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ugawa S., et al.: "Amiloride-Insensitive Currents of the ASIC2a/ASIC2b Heteromeric Sour-Taste Receptor Channel"Journal of Neuroscience. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueda T., et al.: "A novel putative M9.2 isoform of V-ATPase expressed in the nervous system"Neuroreport. 14. 25-30 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ugawa S., et al.: "Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors"J Clin Invest. 110. 1185-1190 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishida Y., et al.: "Vanilloid receptor subtype-1 (VR1) is specifically localized to taste papillae"Mol Brain Res. 107. 17-22 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aihara N., et al.: "Intracerebral hemorrhage upregulates Na(+)/myo-inositol cotransporter in the rat brain"Neurosci Lett. 327. 21-24 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nozaki M., et al.: "Enhanced expression of adhesion molecules of the retinal vascular endothelium in spontaneous diabetic rats"Ophthalmic Res. 34. 158-164 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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