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UEDA Takashi

    Graduate School of Medical Sciences Department of Anatomy and Neuroscience　Associate Professor
Contact： tuedamed.nagoya-cu.ac.jp
Last Updated :2024/04/26

Researcher Information

URL

Research funding number

  • 90244540

J-Global ID

Research Interests

  • TRPチャネル   受容体   生体センサー   

Research Areas

  • Life sciences / Anatomy
  • Life sciences / Neuroanatomy and physiology

Academic & Professional Experience

  • 2010- Associate Professor, Nagoya City University
  • 2006-2010 Assistant Professor, Nagoya City University
  • 1995-2006 Assistant Professor (on-campus), Nagoya City University
  • 1992-1995 Research Associate, Nagoya City University
  • 1986-1991 Researcher, Nagoya City University

Education

  •        - 1986  Fujita Health University

Association Memberships

  • Society for Neuroscience   日本神経化学会   日本神経科学会   日本解剖学会   

Published Papers

Conference Activities & Talks

  • マウス消化管におけるASIC4チャネルの発現  [Not invited]
    植田 高史
    第123回日本解剖学会総会・全国学術集会  2018/03
  • マウス鼻腔上皮におけるTRPV4チャネルの機能発現  [Not invited]
    植田 高史
    第120回日本解剖学会総会・全国学術集会、第92回日本生理学会大会 合同大会  2015/03
  • 下垂体におけるTRPVチャネルの発現と機能解析．  [Not invited]
    第118回日本解剖学会総会  2013
  • 下垂体における浸透圧感受性TRPチャネルの解析．  [Not invited]
    第36回日本神経科学大会/第56回日本神経化学会大会／第23回日本神経回路学会大会・合同大会 (Neuro2013)  2013
  • 神経性下垂体におけるTRPチャネルの機能解析．  [Not invited]
    第35回日本神経科学大会/第55回日本神経化学会大会・合同大会 (Neuro2012)  2012
  • 消化管上皮におけるthermoTRPチャネルの発現と機能解析．  [Not invited]
    第116回日本解剖学会総会  2011
  • ヒト食道上皮細胞における機械刺激とATP放出．  [Not invited]
    第71回日本解剖学会中部支部学術集会  2011
  • ガイソシジンメチルエーテルのセロトニンおよびドーパミン受容体に対する抗精神病薬様作用．  [Not invited]
    第33回日本神経科学大会/第53回日本神経化学会大会・合同大会 (Neuro2010)  2010
  • 食道上皮細胞におけるTRPV4チャネルの発現と機能解析.  [Not invited]
    第70回日本解剖学会中部支部学術集会  2010
  • 遠位大腸粘膜上皮に発現するTRPV3チャネルの解析．  [Not invited]
    第114回日本解剖学会総会  2009
  • Gタンパク質との会合を指標にしたGi共役型受容体アッセイ系の確立．  [Not invited]
    第52回日本神経化学大会  2009
  • Gタンパク質共役型アミノ酸受容体に相同性をもつオーファン受容体の解析．  [Not invited]
    第113回日本解剖学会総会  2008
  • 種々のGタンパク質に共役するセロトニン受容体機能の単一解析法．  [Not invited]
    第51回日本神経化学大会  2008

MISC

Awards & Honors

  • 1996 Young Histochemist Award. The International Federation of Societies of Histochemistry and Cytochemistry.

Research Grants & Projects

  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2027/03 
    Author : 鵜川 眞也; 岩崎 真一; 柴田 泰宏; 島田 昌一; 熊本 奈都子; 村上 信五; 植田 高史
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2022/04 -2025/03 
    Author : 渡辺 正哉; 渋谷 正史; 鵜川 眞也; 植田 高史
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/04 -2021/03 
    Author : Ugawa Shinya
     
    ASICs (acid-sensing ion channels) are putative mechano-gated cation channels in mammals. In the present study, we discovered that at least ASIC1a, ASIC1b, and ASIC4 are expressed in mouse auditory and vestibular hair cells. In particular, transmission electron microscopy revealed that ASIC1b proteins were located at the stereociliary tips, suggesting that all the three ASIC subtypes are somehow involved in the generation of mechanoelectrical transduction (MET) currents. ABR (auditory brainstem response) tests demonstrated the slight-to-moderate degree of deafness in ASIC1b or ASIC4 knockout mice. Further investigations are needed to assess the physiological roles of ASICs in mouse inner ear MET.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/04 -2020/03 
    Author : Kamiya Takeshi
     
    Although acid-sensing ion channel 4 (ASIC4) is a novel mechanical ion channel, the expression and the function in the gastrontestinal (GI) tract is unknown. The aoms of this study was to investigate and the function of ASIC4 in the mouse GI tract. RT-PCR analysis showed that ASIC4 transcripts were obtained from the jejunum to distal colon in adult mice. X-gal staining revealed that ASIC4 was expressed in the myenteric plexus. β-galactosidase activity was foumd in both Ach+ and NOS+ neurons. ASIC4 knock out (KO) mice showed delayed intestinal transit time compared with wild type mice by phenol red method. The ileum of ASIC4-KO mice revealed week response to Ach and high dose nicotine by Magnus assay. These results suggested that ASIC4 may play an important role in GI motor function.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/06 -2019/03 
    Author : Ugawa Shinya
     
    We identified a putative mechanosensory channel ASIC-X in mouse auditory hair cells, and explored its channel properties using a combination of electrophysiology and ratio-imaging techniques with fura-2 and SBFI. Although the leakage currents of heterologously expressed ASIC-X were augmented by strong shear stress, neither hypotonicity nor direct stretching of plasma membrane enhanced the currents. Mechanoelectrical transduction (MET) currents in outer hair cells (OHCs) of ASIC-X knockout mice did not significantly change in the amplitude, compared to MET currents in wild-type OHCs, which is in good agreement with the in vitro data. However, our investigations revealed that the ASIC-X channel was selective to sodium ions. Therefore, ASIC-X is most likely to function as a sodium leak channel in vivo rather than as a mechanosensitive molecule. The tissue distribution of the channel should be clarified in detail next.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/10 -2019/03 
    Author : WATANABE Masaya
     
    To explore the peripheral mechanism of myofascial pain syndrome (MPS), we focused on vascular endothelial growth factor (VEGF), which is released during ischemic state in the affected area of MPS and regulates hypoxia-induced vascular function. Intramuscular administration of VEGF caused acute and subacute mechanical hyperalgesia in mice. This hyperalgesia was improved by intramuscular administration of anti-VEGFR1 antibody or TRPV1 blocker capsazepine. In addition, the VEGF-induced mechanical hyperalgesia was not observed in TRPV1 knockout mice. VEGFR1 co-localized with TRPV1 in mouse dorsal root ganglion neurons. These results suggest that VEGF-induced mechanical hyperalgesia is involved in activation of VEGFR1 and TRPV1 channel. Furthermore, intramuscular saline injection also alleviated the VEGF-induced hyperalgesia. The analgesic effect depended on different concentrations of sodium chloride and 0.15M concentration of saline was the most effective in the present study.
  • 酸感受性イオンチャネルを介した新しい味覚受容機構の解明
    Date (from‐to) : 2015/04 -2019/03 
    Author : 植田 高史
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2017/03 
    Author : SHIKANO Michiko
     
    Acid-sensing ion channel 5 (ASIC5；also called BLINaC or BASIC) is a novel bile acid-sensitive ion channel, which is expressed in the epithelial cells that line bile ducts (Wiemuth et al, 2012), but the expression in the upper digestive tract is unknown. We thus examined the expression of ASIC5 in the mouse esophagus. RT-PCR analysis found that the short fragments of ASIC5 transcripts were abundantly detected in the middle and lower regions. Full length PCR cloning analysis identified a novel splicing variant from the mouse esophagus along with the registered ASIC5 transcripts. We also examined the expression of acid-sensitive G protein-coupled receptor TGR5 known as another candidate in a human normal esophageal epithelial cell line HET-1A, but apparent expression was not detected. ASIC5 may participate in physiological and pathophysiological functions of the esophagus, although the expression of ASIC5 protein was not confirmed because of lack of antibodies specific to ASIC5.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013/04 -2017/03 
    Author : KAMIYA Takeshi; UEDA Takashi
     
    Although acid-sensing ion channel 5 (ASIC5) is a novel bile acid-sensitive ion channel, which is expressed in the bile duct epithelial cells, the expression in the esophagus in unknown. The aim of this study was to investigate the expression of ASIC5 in the mouse esophagus. Reverse transcription polymerase chain reaction (RT-PCR) analysis found that the short fragments of ASIC5 transcripts were abundantly detected in the middle and lower regions. Full length PCR cloning analysis identified a novel splicing variant from the mouse esophagus along with the registered ASIC5 transcripts. We also examine the expression of acid-sensitive G protein-coupled receptor TGR5 known as another candidate in a human normal esophageal epithelial cell line HET-1A, but apparent expression was not detected. ASIC5 may participate in physiological and pathophysiological functions of the esophagus, although the expression of ASIC5 protein was not confirmed because of lack of antibodies specific to ASIC5.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2011/04 -2015/03 
    Author : UGAWA SHINYA; KITAMURA Ken; NOGUCHI Yoshihiro; MURAKAMI Shingo; UEDA Takashi; KAJITA Kenji; SAKUMA Eisuke; KROS Corne
     
    We investigated whether ASIC1b located at the ankle regions of stereocilia in mouse auditory hair cells contributes to normal auditory function, using ASIC1b knockout (KO) mice. Transmission electron microscopy demonstrated that the morphology of inner and outer hair cells of adult KO mice were normal. Patch-clamp experiments showed that immature inner and outer hair cells of wild-type mice generated large inward currents in response to acidic stimuli, and those currents were abolished in the presence of amiloride, an inhibitor of ASIC1b. Proton-induced ASIC-like currents were still detected in inner and outer hair cells of age-matched KO mice, suggesting that other ASIC subtypes also exist in mouse auditory hair cells. We are currently conducting ABR (auditory brainstem response) and DPOAE (distortion product otoacoustic emission) tests to evaluate peripheral auditory function in KO mice. Further experiments are needed to elucidate functional roles of ASIC1b in the stereocilia.
  • 酸感受性イオンチャネルを介した新規内分泌調節機構の解明
    Date (from‐to) : 2012 -2014 
    Author : 植田高史; 鵜川眞也
  • 呼吸上皮に存在する新規CO_2受容体の単離と機能解析
    Date (from‐to) : 2009 -2011 
    Author : 植田高史; 鵜川眞也; 島田昌一
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2007 -2010 
    Author : UGAWA Shinya; SHIMADA Shoichi; UEDA Takashi; MURAKAMI Shingo; ISHIDA Yusuke; KAJITA Kenji; SHIMADA Shoichi; ISHIDA Yusuke
     
    ASIC1b knockout (-/-) mice exhibited significantly elevated ABR (auditory brainstem response) thresholds in the presence of typical inner ear histology. Mechano-electrical transducer currents were slightly reduced in the outer hair cells.
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2007 -2008 
    Author : 石田 雄介; 鵜川 眞也; 植田 高史; 島田 昌一; 田中 克幸; 梶田 健二
     
    本研究の目的は、味覚経路に発現する温度感受性TRPが中枢ではなくすでに末梢のレベルで味覚に影響を及ぼすことを証明し、更にその影響を解析することである。この研究は昨年度から引き続き行われており、以下に本年度の成果とその重要性について説明する。(1)トレーサーFast Bluev (FB)による舌を支配する鼓索神経の標識:当初トレーサーにはDiOを考えていたが、実際に使用して比較してみるとFBによる標識のほうがコントラストもよく調子が良かった。マウス舌前方(鼓索神経領域)にFBを局注し、舌に分布する神経線維を順行性にトレースすることで舌を支配する膝神経節の神経細胞体を同定できた。(2)マウス膝神経節における温度感受性TRP (TRPV1)の発現:昨年度の研究から、マウス膝神経節において温度感受性TRP蛋白のひとつTRPV1が発現していることが示唆されていた。トレーサーFBを用いて舌を支配する膝神経節の細胞体を同定した上で、TRPV1の免疫染色を行ったところこれらのシグナルは一部重なっていた。以上の結果から味覚伝達経路にはTRPV1が発現していることが示唆された。(3)さまざまな温度の味溶液で舌を刺激した場合に誘発される鼓索神経応答の電気生理学的検討:舌を刺激する五つの味溶液(甘味・酸味・苦味・うま味・塩味)を用意し、さらにそれらの温度を低いものから高いものまで設定して、鼓索神経whole nerve recordingを行った。その結果、一般的に42℃(高温)、100℃(低温)では舌の表面温度である25QCよりも活性が抑制された。しかし塩味の場合は10℃では同様に25℃よりも活性が抑制されたが、TRPV1が活性化する42℃の高温条件ではむしろ鼓索神経の応答は増強された。このことから高温下ではTRPV1が活性化して(後、何らかのメカニズムを経て)塩味による味覚神経の応答を増強することが示唆された。
  • 新規CO_2受容器の同定およびその分子基盤に関する研究
    Date (from‐to) : 2003 -2005 
    Author : 植田高史; 鵜川眞也; 島田昌一
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2002 -2005 
    Author : SHIMADA Shoichi; MURAKAMI Shingo; UGAWA Shinya
     
    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.
  • Gタンパク質共役型味覚受容体遺伝子の単離および解析
    Date (from‐to) : 2002 -2005 
    Author : 植田高史; 鵜川眞也; 島田昌一; 藤森修; 平林義章
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2002 -2004 
    Author : 鵜川 眞也; 島田 昌一; 植田 高史
     
    ヒト三叉神経節から新しい水素イオン感受性チャンネルをスクリーニングしたところ、上皮型アミロライド感受性イオンチャンネルファミリーに属するENaC-delta(epithelial Na channel-delta)が単離された。アフリカツメガエル卵母細胞発現系を用いて電気生理学的に解析したところ、水素イオンによって活性化されることが確認された。ASIC(acid-sensing ion channel)やVR1(transient receptor potential subtype-1)と同様に、末梢の痛覚受容器において炎症やリュウマチなどの局所的なアシドーシスに伴う痛みの発生に寄与していると考えられたので、三叉神経節における分布をin situ hybridization法および免疫組織化学法を用いて検討したが、特異的なシグナルは検出できなかった。しかしながら、ヒトの大脳皮質、小脳における発現をNorthern blot法を用いて調べたところ、両者に強く発現していることが確認できた。脳におけるENaC-deltaの役割は今のところ不明であるが、この遺伝子は霊長類以上のほ乳動物にしか発現していないことから、高次脳機能との関連が考えられ、現在も脳における詳細な分布パターンの解析を行っている。また、このイオンチャンネルがVR1のアンタゴニストであるカプサゼピンにより活性化することを我々は見出したので、ヒトの神経系におけるカプサゼピンの効果について詳しく検索しているところである。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2001 -2003 
    Author : UGAWA Shinya; HIRABAYASHI Yoshifumi; FUJIMORI Osamu; SHIMADA Shoichi; UEDA Takashi
     
    Acid-sensing ion channel-2a (ASIC2a) is an amiloride-blockable proton-gated action channel, probably contribution to sour-taste detection in rat taste cells. To isolate another subtype of the sour-taste receptor, we screened a rat circumvallate papilla cDNA library and identified ASIC2b, an N-terminal splice variant of ASICA2a. Reverse transcription-polymerase chain reaction analyses confirmed the expression of ASIC2b transcripts in the circumvallate papilla and, moreover, demonstrated its expression in the foliate and fungiform papillae. Immunohistochemical analyses revealed that ASIC2b, as well as ASIC2a, was expressed in a subpopulation of taste cells in the circumvallate, foliate, and fungiform papillae, and some of the cells displayed both ASIC2a-and ASIC2b-immunoreactivities. Subsequent co-immunoprecipitation studies with circumvallate papillae extracts indicated that ASIC2b associated with ASIC2a to form assemblies, and, together with our immunohistochemical findings, strongly suggested that both ASIC2 subunits formed heteromeric channels in taste cells in the circumvallate, foliate, and fungiform papillae. Oocyte electro-physiology demonstrated that the ASIC2a/ASIC2b channel generated maximal inward currents at pH 2.0, which is in good agreement with the in vivo pH-sensitivity of rat taste cells, and that the amiloride-sensitivity of the heteromer decreased with decreasing pH and was almost completely abolished at pH 2.0. These findings provide persuasive explanations for the amiloride-insensitivity of acid-induced responses of rat taste cells.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2000 -2002 
    Author : SHIMADA Shoichi; UEDA Takashi; HIRABAYASHI Yoshifumi; MURAKAMI Shingo; UGAWA Shinya
     
    Acid-sensing ion channel-2a (ASIC2a) is an amiloride-blockable proton-gated cation channel, probably contributing to sour-taste detection in rat taste cells. To isolate another subtype of the sour-taste receptor, we screened a rat circumvallate papilla cDNA library and identified ASIC2b, an N-terminal splice variant of ASIC2a, Reverse transcription-polymerase chain reaction analyses confirmed the expression of ASIC2b transcripts in the circumballate papilla and, moreover, demonstrated its expression in the foliate and fungiform papillae. Immunohistochemical analyses revealed that ASIC2b, as well as ASIC2a, was expressed in a subpopulation of taste cells in the circumvallate, foliate, and fungiform papillae, and some of the cells displayed both ASIC2a-and ASIC2b-immunoreactivities. Subsequent co-immunoprecipitation studies with circumvallate papillae extracts indicated that ASIC2b associated with ASIC2a to form assemblies, and, together with our immunohistochemical findings, strongly suggested that both ASIC2 subunits formed heteromeric channels in taste cells in the circumvallate, foliate, and fungiform papillae. Oocyte electrophysiology demonstrated that the ASIC2a/ASIC2b channel generated maximal in ward currents at pH 2.0, which is in good agreement with the in vivo pH-sensitivity of rat taste cells, and that the amiloride-sensitivity of the heteromer decreased with decreasing pH and was almost completely abolished at pH 2.0. These findings provide persuasive explanations for the amiloride-insensitivity of acid-induced responses of rat taste cells.
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 1999 -2000 
    Author : 島田 昌一; 鵜川 眞也; 植田 高史
     
    本研究はMDEG1イオンチャネルの第二膜貫通部位に人工的な点変異を導入し、この陽イオンチャネルが開いたまま閉じない状態を作り出し、このgain of functionの特殊なチャネルをトランスジェニックマウスに発現させて、味覚障害や神経変性症のモデル動物を作成することが目的である。 MDEG1の430番目のグリシン残基をPCR法を用いて様々なアミノ酸に置換し、電気生理学的に解析した結果、フェニルアラニンに置換させたものが最も効果的にチャネルが開いたままの状態になることを明らかにした。さらにミュータントイオンチャネル(MDEG1-G430F)を発現させた細胞に、選択的な細胞死が起こることを確認した。このMDEG1-G430FのcDNAにopsinのプロモーター・エンハンサー領域をつなげて岡部らと共同研究でトランスジェニックマウスを作成した。現在そのトランスジェニックマウスがどの様な障害をきたしたか、形態学的、生理学的な解析を進めている。 また、堀本らと共同研究で、このMDEG1-G430Fミュータントに、がん特異的プロモーターを組み込んだものを、リポゾーム法を用いて、転移がんモデルマウスに投与し、がん細胞の選択的な細胞死を引き起こすモデルマウスを作成した。
  • 神経 特異的新規V-ATPaseサブユニットの解析
    Date (from‐to) : 1999 -2000 
    Author : 植田高史
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 1998 -2000 
    Author : SHIMADA Shoichi; UEDA Takashi; HIRABAYASHI Yoshifumi; FUJIMORI Osamu; UGAWA Shinya
     
    We have identifieda cDNA encoding a taste receptor for sourness (MDEG1) from a rat circumvallate papilla cDNA library by combined cDNA homology and functional expression approaches. When expressed in Xenopus laevis oocytes, MDEG1 showed characteristics of a proton-gated amiloride-sensitive cation channel. Interestingly, acidic stimulation by acetic acid, the chief ingredient of vinegar, generatedlarger inwardcurrents than that by hydrochloric acidat equal pH.In situ hybridization revealed that the mRNA of MDEG1 was exclusively localized in taste buds. MDEG1 immunoreactivity was found on the cell surface and in the apical portion of taste bud cells, especially in type III cells which are classifiedas gustatory receptor cells. This is the first taste receptor cDNA to be cloned. To isolate another subunit of the sour-taste receptor, we screened a rat circumvallate papilla cDNA library and iden tified MDEG2. Immunohistochemical and electrophysiological studies demonstrated that MDEG2 formed heterooligomeric channels with MDIEG1 at the apical portion of single taste-cells and modified the desensitization of MDEG1 channel. The desensitization rate of the heterooligomer was dramatically altered by a single amino acid substitution of Gly481 in MDEG2 without changing other channel properties. These findings suggest that MDEG2 regulates the sour-taste receptor desensitization contributing to sour-taste adaptation and that Gly481 in MDEG2 is the key amino acidresidue that controls the duration of sourtaste sensation.

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