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Publications

"Gene expression profiling of α-gustducin-expressing taste cells in mouse fungiform and circumvallate papillae."
Yamada Y, Takai S, Watanabe Y, Osaki A, Kawabata Y, Oike A, Hirayama A, Iwata S, Sanematsu K, Tabata S, Shigemura N.
BBRC. 2021, 557:206-212

味覚の大きな謎である甘味細胞 or 苦味細胞への分化・運命決定メカニズムの解明を目指し、味覚特異的Gタンパク質Gustducin(甘味または苦味細胞マーカー)に蛍光GFPを発現するマウスを用いて、GFP発現味細胞をFACSで単離し、単一細胞RNA-seq解析により甘味細胞または苦味細胞に特異的に発現する遺伝子を炙り出しました。将来、この中の遺伝子を操作することで、味覚障害に苦しんでいる患者さんに、美味しい味覚を取り戻してあげることが出来るようになるかもしれません。

"Drinking Ice-cold Water Reduces the Severity of Anticancer Drug-induced Taste Dysfunction in Mice."
Osaki A, Sanematsu K, Yamazoe J, Hirose F, Watanabe Y, Kawabata Y, Oike A, Hirayama A, Yamada Y, Iwata S, Takai S, Wada N, Shigemura N.
Int J Mol Sci. 2020, 21(23), 8958

抗がん剤の服用により、患者様の50-70%がその副作用の味覚障害に苦しんでいます。本研究では、マウスをもちいて、抗がん剤による味覚障害発症の分子メカニズムを調べました。この結果、抗がん剤投与により、口腔のある特定の(寿命の短い)味細胞がダメージを受けやすく細胞死を起こし、その味神経の応答が有意に低下していることを明らかにしました。さらに、この味覚障害が、氷水を用いた経口冷却療法により軽減されることを世界に先駆けて実証しました。この方法は、副作用やストレスがほとんどなく、コストもかからない方法であるため、近い将来、臨床現場において「アイスキューブ」や「アイスクリーム」を使った新たな味覚障害予防法として採用されることが期待されます。

"Identification of characteristic compounds of moderate volatility in breast cancer cell lines."
Tanaka M, Hsuan C, Oeki M, Shen W, Goda A, Tahara Y, Onodera T, Sanematsu K, Rikitake T, Oki E, Ninomiya Y, Kurebayashi R, Sonoda H, Maehara Y, Toko K, Matsui T.
PLoS One 2020 Jun 29;15(6):e0235442.

乳がん細胞株で高排出される中鎖不飽和脂肪酸の同定に成功。私たちが参画している九州大学五感応用デバイス研究開発センター(センター長:大学院農学研究院 松井利郎教授)は、正常細胞株に比べて、乳がん細胞株の培養液に高濃度に存在する複数の中鎖不飽和脂肪酸の同定に成功しました。また、これらの中鎖不飽和脂肪酸は、がん患者呼気に含まれる特徴的なにおい成分へと酸化分解されたことから、がん患者特有の呼気臭の発生との関連が推察され、乳がん診断用バイオマーカーとして応用されることが期待されます。

"Effects of bitter receptor antagonists on behavioral lick responses of mice."
Masamoto M, Mitoh Y, Kobashi M, Shigemura N, Yoshida R.
Neurosci Lett. 2020 Jun 21;730:135041

苦味受容体のヒトとマウス間種差を薬理学的、行動生理学的に明らかにしました。岡山大学の吉田竜介教授(2018年当研究室准教授)の研究成果です。

"Insulin Function in Peripheral Taste Organ Homeostasis."
Takai S, Shigemura N.
Curr Oral Health Rep. 2020 Mar

血糖値を下げるホルモン・インスリンが味覚器にも直接作用して味細胞の分化や増殖に関与していることを報告しましたが、さらにその関連情報や、特に糖尿病と味覚障害との関連をまとめたreviewです。

"Expression of protocadherin-20 in mouse taste buds."
Hirose F, Takai S, Takahashi I, Shigemura N.
Sci Rep. 2020 Feb 6;10(1):2051.

舌の表面で味を感じる味細胞の寿命は約10日と短いです。それにも関わらず、味覚情報(認知)は恒常的に維持されています。このことは、味細胞と味神経とは、私たちが生まれてから死ぬまでの全ライフコースを通して絶えずダイナミックに配線/断線を繰り返しながら、さらに味質選択的に正確に配線されることにより達成されていると考えられます。本研究では、接着因子であるプロトカドヘリン20が甘味・うま味細胞と神経に発現して、その味質選択的な配線に関与している可能性を示唆しました。この配線メカニズムが加齢や病気で上手く働かなくなることで、甘いものが苦い??など味覚障害が生じてしまう可能性が考えられました。

"Effects of insulin signaling on mouse taste cell proliferation."
Takai S, Watanabe Y, Sanematsu K, Yoshida R, Margolskee RF, Jiang P, Atsuta I, Koyano K, Ninomiya Y, Shigemura N.
PLoS One. 2019 Nov 12;14(11):e0225190.

インスリンは血糖値を下げる役割を担う重要なホルモンです。このインスリンの受容体が、なんと口腔の味細胞にも発現していることを明らかにしました。さらに最先端の技術である「味蕾オルガノイド(試験管で作るミニ臓器)」を用いて、インスリンによる効果を調べたところ、高濃度のインスリンにより味蕾の大きさが小さくなり、味細胞の数が減ることを発見しました。これらのことからインスリンは味蕾の成長に関与していることが分かりました。糖尿病では味覚感受性が低下しているという報告もありますが、その原因にこのインスリンの作用が関与しているのかもしれません。

"Expression of Renin-Angiotensin System Components in the Taste Organ of Mice."
Shigemura N, Takai S, Hirose F, Yoshida R, Sanematsu K, Ninomiya Y.
Nutrients. 2019 Sep 19;11(9). pii: E2251.

体内Naホメオスタシス維持を司るレニン-アンジオテンシン系が全身循環系だけでなく、なんと口腔の味覚器でも独立して機能していることを明らかにしました。外部環境(食事中や唾液成分の変化など)に応じて、短時間でNaを効率よく摂取するための塩味感受性の変化が味覚器で起こっている可能性が示唆されました。過剰な塩分の取りすぎや過少な摂取にならないように、口腔が前もって準備しているのかもしれません。

"Structural architecture of a dimeric class C GPCR based on co-trafficking of sweet taste receptor subunits."
Park J, Selvam B, Sanematsu K, Shigemura N, Shukla D, Procko E.
J Biol Chem. 2019 Feb 5. pii: jbc.RA118.006173.

甘味受容体T1R2/T1R3ヘテロ二量体の分子構造と膜移行・二量体形成・活性との相関を明らかにしました。T1Rsは創薬ターゲットとされているGPCRクラスCのメンバーであるため、本知見が肥満や糖尿病などに対する創薬開発へ応用されることが期待されます。JBCの表紙を飾りました。

"Diurnal Variation of Sweet Taste Recognition Thresholds Is Absent in Overweight and Obese Humans."
Sanematsu K, Nakamura Y, Nomura M, Shigemura N, Ninomiya Y.
Nutrients. 2018 Mar 2;10(3). pii: E297. doi: 10.3390/nu10030297.

"Bitter taste responses of gustducin-positive taste cells in mouse fungiform and circumvallate papillae."
Yoshida R, Takai S, Sanematsu K, Margolskee RF, Shigemura N, Ninomiya Y.
Neuroscience. 2017 Nov 4. pii: S0306-4522(17)30784-4.

"Oral lipase activities and fat-taste receptors for fat-taste sensing in chickens."
Kawabata Y, Kawabata F, Nishimura S, Tabata S.
Biochem Biophys Res Commun. 2017 Nov 4. pii: S0006-291X(17)32105-8.

"The role of cholecystokinin in peripheral taste signaling in mice."
Yoshida R, Shin M, Yasumatsu K, Takai S, Inoue M, Shigemura N, Takiguchi S, Nakamura S, Ninomiya Y
Frontiers in Physiology

"Binding properties between human sweet receptor and sweet-inhibitor, gymnemic acids."
Sanematsu K, Shigemura N, Ninomiya Y
J Oral Biosci 2017:59(3)127-30.

實松助教が歯科基礎医学会学会奨励賞の受賞内容をまとめました。ギムネマという植物の葉に含まれるギムネマ酸は、ヒトの甘味を抑制します。飴玉を舐めても全く味のしない石を舐めてるように感じます。その不思議を、甘味受容体の再構築系および分子モデリングを駆使して解明しました。この知見を応用することにより、肥満や糖尿病に対する新たな甘味調節を介した予防・治療法が開発される可能性があります。
 

"Taste Sensing Systems Influencing Metabolic Consequences."
Shigemura N.
Current Oral Health Reports 2017:4(2)79-86.

 塩味の受容機構とその調節機構について、さらに高血圧の薬と塩味感受性の変化との関連をまとめました。アンジオテンシンIIは、体内のナトリウム量が減った時に分泌が増える血圧調節ホルモンとしてよく知られています。このアンジオテンシンIIが口腔の味細胞にも直接作用して、塩味を抑制することで塩分の摂取量を増やすことが明らかになってきました。さらに、同時に甘味を強めることでカロリー摂取量を増やす可能性も見えてきました。「スイカに塩」、「ぜんざいに塩」、「ポカリスエットの塩分」など、甘味に塩を加えることで私たちはそれらをより美味しく好ましく感じます。この体内に取り込む最適な塩分とカロリー量を決めているのが、味覚に働くアンジオテンシンIIかもしれません。
 

"Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells."
Jyotaki M, Sanematsu K, Shigemura N, Yoshida R, Ninomiya Y.
Neuroscience. 2016:S0306-4522(16)30275-5.

 レプチンは肥満抑制ホルモンであり、主に脳に作用して摂食を抑制することがよく知られています。また、口腔の味細胞にも作用して甘味応答を特異的に抑制することも明らかとなっていました。本研究では、このレプチンが消化管内分泌培養細胞(甘味受容体発現)にも作用して甘味応答を抑制し、さらに同細胞からのインクレチン・GLP-1(インスリン分泌促進因子)の放出を抑制することを明らかにしました。このことから、レプチンは中枢と味細胞での機能に加えて、消化管では糖吸収の抑制にも関与することで肥満を抑制している可能性が示唆されました。
 

"Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides."
Sukumaran SK, Yee KK, Iwata S, Kotha R, Quezada-Calvillo R, Nichols BL, Mohan S, Pinto BM, Shigemura N, Ninomiya Y, Margolskee RF.
Proc Natl Acad Sci U S A. 2016:113(21):6035-40.

 ショ糖などの二糖類は消化管において二糖類分解酵素により単糖類(グルコースなど)に分解されてから吸収されます。本研究では、この二糖類分解酵素が口腔の味細胞でも働いており、舌上で単糖類をつくることで甘味を引き出すことを明らかにしました。この口腔でグルコースを感知するのも消化管で糖吸収の役割を担う糖輸送体GLUT/SGLTであると考えられています。これらのことから、口と消化管は同じ分子を使いながら糖感知と糖吸収を使い分け、さらにこれらの機能を連携させることで体内グルコースバランスを巧妙に調節している可能性が示唆されました。

"Intracellular acidification is required for full activation of the sweet taste receptor by miraculin."
Sanematsu K, Kitagawa M, Yoshida R, Nirasawa S, Shigemura N, Ninomiya Y.
Sci Rep. 2016 6:22807

 ミラクリンは西アフリカ原産の果物ミラクルフルーツの成分で、古くから酸っぱいものを甘くする作用があることが知られていました(不味いお酒を美味しく飲むために利用!?)。しかし、その分子メカニズムについては不明でした。本研究では、このミラクリンが、舌の甘味受容細胞に発現する甘味受容体T1R2/T1R3に結合すること、さらに外からの酸刺激および細胞内酸性度により、T1R2/T1R3の構造変化と活性化が起こり、より強い甘味応答が起こることを明らかにしました。甘味受容体は肥満や糖尿病との関連が示唆されています。この知見を応用することにより甘味受容体を介した新たな予防・治療法が開発される可能性があります。

"Recent Advances in Molecular Mechanisms of Taste Signaling and Modifying."
Shigemura N, Ninomiya Y.
Int Rev Cell Mol Biol. 2016;323:71-106.

 近年、急速に明らかになりつつある味覚受容および修飾機構の新知見をまとめました。

"Taste information derived from T1R-expressing taste cells in mice."
Yoshida R, Ninomiya Y.
Biochem J. 2016 Mar 1;473(5):525-36.

"The function of glucagon-like peptide-1 in the mouse peripheral taste system."
Takai S, Yoshida R, Yasumatsu K, Shigemura N, Ninomiya Y.
Journal of Oral Bioscience. 58: 10-15, 2016

"Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds."
Yoshida R, Noguchi K, Shigemura N, Jyotaki M, Takahashi I, Margolskee RF, Ninomiya Y.
Diabetes. 2015 Nov;64(11):3751-62.

"Angiotensin II and taste sensitivity."
Shigemura N.
Jap Dent Sci Rev. 2015;51(2):51-58.

"High resolution time-intensity recording with synchronized solution delivery system for the human dynamic taste perception."
Goto TK, Yeung AW, Suen JL, Fong BS, Ninomiya Y.
J Neurosci Methods. 2015 Apr 30;245:147-55.

"Modulation of taste responsiveness by angiotensin II"
Shigemura N.
Food Sci and Tech Res 2015;21(6):757-764.

"Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice."
Niki M, Jyotaki M, Yoshida R, Yasumatsu K, Shigemura N, DiPatrizio NV, Piomelli D, Ninomiya Y.
J Physiol. 2015 Jun 1;593(11):2527-45.

"Glucagon-like peptide-1 is specifically involved in sweet taste transmission."
Takai S, Yasumatsu K, Inoue M, Iwata S, Yoshida R, Shigemura N, Yanagawa Y, Drucker DJ, Margolskee RF, Ninomiya Y.
FASEB J. 2015 Jun;29(6):2268-80.

"Involvement of multiple taste receptors in umami taste: analysis of gustatory nerve responses in metabotropic glutamate receptor 4 knockout mice."
Yasumatsu K, Manabe T, Yoshida R, Iwatsuki K, Uneyama H, Takahashi I, Ninomiya Y.
J Physiol. 2015 Feb 15;593(4):1021-34.

"Structure, function, and signaling of taste G-protein-coupled receptors."
Sanematsu K, Yoshida R, Shigemura N, Ninomiya Y.
Curr Pharm Biotechnol. 2014;15(10):951-61.

"Molecular mechanisms for sweet-suppressing effect of gymnemic acids."
Sanematsu K, Kusakabe Y, Shigemura N, Hirokawa T, Nakamura S, Imoto T, Ninomiya Y.
J Biol Chem. 2014 Sep 12;289(37):25711-20.

"Expression of the glucose-sensing receptor T1R3 in pancreatic islet: changes in the expression levels in various nutritional and metabolic states."
Medina A, Nakagawa Y, Ma J, Li L, Hamano K, Akimoto T, Ninomiya Y, Kojima I.
Endocr J. 2014;61(8):797-805.

"Multimodal function of the sweet taste receptor expressed in pancreatic β-cells: generation of diverse patterns of intracellular signals by sweet agonists."
Nakagawa Y, Nagasawa M, Mogami H, Lohse M, Ninomiya Y, Kojima I.
Endocr J. 2013;60(10):1191-206.

"Taste transductions in taste receptor cells: basic tastes and moreover."
Iwata S, Yoshida R, Ninomiya Y.
Curr Pharm Des. 2014;20(16):2684-92. Review.

"Activation of tongue-expressed GPR40 and GPR120 by non caloric agonists is not sufficient to drive preference in mice."
Godinot N, Yasumatsu K, Barcos ME, Pineau N, Ledda M, Viton F, Ninomiya Y, le Coutre J, Damak S.
Neuroscience. 2013 Oct 10;250:20-30.

"Angiotensin II Modulates Salty and Sweet Taste Sensitivities."
Shigemura N, Iwata S, Yasumatsu K, Ohkuri T, Horio N, Sanematsu K, Yoshida R, Margolskee RF, Ninomiya Y.
J Neurosci. 2013 Apr 10;33(15):6267-77.

"Taste responses in mice lacking taste receptor subunit T1R1."
Kusuhara Y, Yoshida R, Ohkuri T, Yasumatsu K, Voigt A, Hubner S, Maeda K, Boehm U, Meyerhof W, Ninomiya Y.
J Physiol. 2013 Apr 1;591(Pt 7):1967-85.

"Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion."
Daly K, Al-Rammahi M, Moran A, Marcello M, Ninomiya Y, Shirazi-Beechey SP.
Am J Physiol Gastrointest Liver Physiol. 2013 Feb 1;304(3):G271-82.

"Modulation of sweet responses of taste receptor cells."
Yoshida R, Niki M, Jyotaki M, Sanematsu K, Shigemura N, Ninomiya Y.
Semin Cell Dev Biol. 2013 Mar;24(3):226-31.

"Gustatory sensation of (L)- and (D)-amino acids in humans."
Kawai M, Sekine-Hayakawa Y, Okiyama A, Ninomiya Y.
Amino Acids. 2012 Dec;43(6):2349-58.

"Expression of sweet receptor components in equine small intestine: relevance to intestinal glucose transport."
Daly K, Al-Rammahi M, Arora DK, Moran AW, Proudman CJ, Ninomiya Y, Shirazi-Beechey SP.
Am J Physiol Regul Integr Comp Physiol. 2012 Jul 15;303(2):R199-208.

"The temporal change in the cortical activations due to salty and sweet tastes in humans: fMRI and time-intensity sensory evaluation."
Nakamura Y, Goto TK, Tokumori K, Yoshiura T, Kobayashi K, Nakamura Y, Honda H, Ninomiya Y, Yoshiura K.
Neuroreport. 2012 Apr 18;23(6):400-4.

"Residual chemoresponsiveness to acids in the superior laryngeal nerve in "taste-blind" (P2X2/P2X3 double-KO) mice."
Ohkuri T, Horio N, Stratford JM, Finger TE, Ninomiya Y.
Chem Senses. 2012 Jul;37(6):523-32.

"Umami taste in mice uses multiple receptors and transduction pathways."
Yasumatsu K, Ogiwara Y, Takai S, Yoshida R, Iwatsuki K, Torii K, Margolskee RF, Ninomiya Y.
J Physiol. 2012 Mar 1;590(Pt 5):1155-70

"Gα-gustducin is extensively coexpressed with sweet and bitter taste receptors in both the soft palate and fungiform papillae but has a different functional significance."
Tomonari H, Miura H, Nakayama A, Matsumura E, Ooki M, Ninomiya Y, Harada S.
Chem Senses. 2012 Mar;37(3):241-51.

"Behavioral responses to glutamate receptor agonists and antagonists implicate the involvement of brain-expressed mGluR4 and mGluR1 in taste transduction for umami in mice."
Nakashima K, Eddy MC, Katsukawa H, Delay ER, Ninomiya Y.
Physiol Behav. 2012 Feb 1;105(3):709-19.

"Localization of brain activation by umami taste in humans."
Nakamura Y, Goto TK, Tokumori K, Yoshiura T, Kobayashi K, Nakamura Y, Honda H, Ninomiya Y, Yoshiura K.
Brain Res. 2011 Aug 11;1406:18-29.

"Sour taste responses in mice lacking PKD channels."
Horio N, Yoshida R, Yasumatsu K, Yanagawa Y, Ishimaru Y, Matsunami H, Ninomiya Y.
PLoS One. 2011;6(5):e20007.

"Responses to apical and basolateral application of glutamate in mouse fungiform taste cells with action potentials."
Niki M, Takai S, Kusuhara Y, Ninomiya Y, Yoshida R.
Cell Mol Neurobiol. 2011 Oct;31(7):1033-40.

"Gustatory signaling in the periphery: detection, transmission, and modulation of taste information."
Niki M, Yoshida R, Takai S, Ninomiya Y.
Biol Pharm Bull. 2010;33(11):1772-7.

"REEP2 enhances sweet receptor function by recruitment to lipid rafts."
Ilegems E, Iwatsuki K, Kokrashvili Z, Benard O, Ninomiya Y, Margolskee RF.
J Neurosci. 2010 Oct 13;30(41):13774-83.

"Reciprocal modulation of sweet taste by leptin and endocannabinoids."
Niki M, Jyotaki M, Yoshida R, Ninomiya Y.
Results Probl Cell Differ. 2010;52:101-14.

"New insights into the signal transmission from taste cells to gustatory nerve fibers."
Yoshida R, Ninomiya Y.
Int Rev Cell Mol Biol. 2010;279:101-34.

"Taste preference for fatty acids is mediated by GPR40 and GPR120."
Cartoni C, Yasumatsu K, Ohkuri T, Shigemura N, Yoshida R, Godinot N, le Coutre J, Ninomiya Y, Damak S.
J Neurosci. 2010;30(25):8376-82.

"Action potential-enhanced ATP release from taste cells through hemichannels."
Murata Y, Yasuo T, Yoshida R, Obata K, Yanagawa Y, Margolskee RF, Ninomiya Y.
J Neurophysiol. 2010;104(2):896-901.

"Modulation of sweet taste sensitivity by orexigenic and anorexigenic factors."
Jyotaki M, Shigemura N, Ninomiya Y.
Endocr J. 2010;57(6):467-75.

"New frontiers in gut nutrient sensor research: nutrient sensors in the gastrointestinal tract: modulation of sweet taste sensitivity by leptin."
Horio N, Jyotaki M, Yoshida R, Sanematsu K, Shigemura N, Ninomiya Y.
J Pharmacol Sci. 2010 Jan;112(1):8-12.

"Endocannabinoids selectively enhance sweet taste."
Yoshida R, Ohkuri T, Jyotaki M, Yasuo T, Horio N, Yasumatsu K, Sanematsu K, Shigemura N, Yamamoto T, Margolskee RF, Ninomiya Y.
Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):935-9.

"Genetically-increased taste cell population with Galpha-gustducin-coupled sweet receptors is associated with increase of gurmarin-sensitive taste nerve fibers in mice."
Yasumatsu K, Ohkuri T, Sanematsu K, Shigemura N, Katsukawa H, Sako N, Ninomiya Y.
BMC Neurosci. 2009 Dec 22;10(1):152.

"The role of transient receptor potential vanilloid-1 on neural responses to acids by the chorda tympani, glossopharyngeal and superior laryngeal nerves in mice."
Arai T, Ohkuri T, Yasumatsu K, Kaga T, Ninomiya Y.
Neuroscience. 2009 Dec 1.

"Multiple Umami Receptors and Their Variants in Human and Mice."
Jyotaki M, Shigemura N, Ninomiya Y.
JOURNAL OF HEALTH SCIENCE 2009 OCT;55(5): 674-81

"Genetic and molecular basis of individual differences in human umami taste perception."
Shigemura N, Shirosaki S, Sanematsu K, Yoshida R, Ninomiya Y.
PLoS One. 2009 Aug 21;4(8):e6717.

"Modulation and transmission of sweet taste information for energy homeostasis."
Sanematsu K, Horio N, Murata Y, Yoshida R, Ohkuri T, Shigemura N, Ninomiya Y.
Ann N Y Acad Sci. 2009 Jul;1170:102-6.

"Multiple receptor systems for umami taste in mice."
Yoshida R, Yasumatsu K, Shirosaki S, Jyotaki M, Horio N, Murata Y, Shigemura N, Nakashima K, Ninomiya Y.
Ann N Y Acad Sci. 2009 Jul;1170:51-4.

"Variation in umami perception and in candidate genes for the umami receptor in mice and humans."
Shigemura N, Shirosaki S, Ohkuri T, Sanematsu K, Islam AS, Ogiwara Y, Kawai M, Yoshida R, Ninomiya Y.
Am J Clin Nutr. 2009 Sep 90(3):764S-769S.

"Discrimination of taste qualities among mouse fungiform taste bud cells."
Yoshida R, Miyauchi A, Yasuo T, Jyotaki M, Murata Y, Yasumatsu K, Shigemura N, Yanagawa Y, Obata K, Ueno H, Margolskee RF, Ninomiya Y.
J Physiol. 2009 Jul 21.

"Multiple receptors underlie glutamate taste responses in mice."
Yasumatsu K, Horio N, Murata Y, Shirosaki S, Ohkuri T, Yoshida R, Ninomiya Y.
Am J Clin Nutr. 2009 Sep;90(3):747S-752S.

"Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion."
Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I.
PLoS One. 2009;4(4):e5106. Epub 2009 Apr 8.

"Multiple sweet receptors and transduction pathways revealed in knockout mice by temperature dependence and gurmarin sensitivity."
Ohkuri T, Yasumatsu K, Horio N, Jyotaki M, Margolskee RF, Ninomiya Y.
Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R960-71.

"NaCl responsive taste cells in the mouse fungiform taste buds."
Yoshida R, Horio N, Murata Y, Yasumatsu K, Shigemura N, Ninomiya Y.
Neuroscience. 2009 Mar 17;159(2):795-803.

"Multiple receptor systems for glutamate detection in the taste organ."
Yasuo T, Kusuhara Y, Yasumatsu K, Ninomiya Y.
Biol Pharm Bull. 2008 Oct;31(10):1833-7. Review.

"G alpha14 is a candidate mediator of sweet/umami signal transduction in the posterior region of the mouse tongue."
Shindo Y, Miura H, Carninci P, Kawai J, Hayashizaki Y, Ninomiya Y, Hino A, Kanda T, Kusakabe Y.
Biochem Biophys Res Commun. 2008 Nov 21;376(3):504-8. Epub 2008 Sep 16.

"Diurnal variation of human sweet taste recognition thresholds is correlated with plasma leptin levels."
Nakamura Y, Sanematsu K, Ohta R, Shirosaki S, Koyano K, Nonaka K, Shigemura N, Ninomiya Y.
Diabetes. 2008 Oct;57(10):2661-5.

"The development of a novel automated taste stimulus delivery system for fMRI studies on the human cortical segregation of taste."
Kami YN, Goto TK, Tokumori K, Yoshiura T, Kobayashi K, Nakamura Y, Honda H, Ninomiya Y, Yoshiura K.
J Neurosci Methods. 2008 Jul 15;172(1):48-53.

"Gurmarin sensitivity of sweet taste responses is associated with co-expression patterns of T1r2, T1r3, and gustducin."
Shigemura N, Nakao K, Yasuo T, Murata Y, Yasumatsu K, Nakashima A, Katsukawa H, Sako N, Ninomiya Y.
Biochem Biophys Res Commun. 2008 Mar 7;367(2):356-63. Epub 2008 Jan 2.

"The taste transduction channel TRPM5 is a locus for bitter-sweet taste interactions."
Talavera K, Yasumatsu K, Yoshida R, Margolskee RF, Voets T, Ninomiya Y, Nilius B.
FASEB J. 2008 May;22(5):1343-55. Epub 2007 Dec 10.

"Amiloride-sensitive NaCl taste responses are associated with genetic variation of ENaC alpha subunit in mice."
Shigemura N, Ohkuri T, Sadamitsu C, Yasumatsu K, Yoshida R, Beauchamp GK, Bachmanov AA, Ninomiya Y.
Am J Physiol Regul Integr Comp Physiol. 2008 Jan;294(1):R66-75. Epub 2007 Oct 31.

"Abnormal taste perception in mice lacking the type 3 inositol 1, 4, 5-trisphosphate receptor."
Hisatsune C, Yasumatsu K, Takahashi-Iwanaga H, Ogawa N, Kuroda Y, Yoshida R, Ninomiya Y, Mikoshiba K.
J Biol Chem. 2007 Dec 21;282(51):37225-31. Epub 2007 Oct 9.

"T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1."
Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E, Daly K, Maillet EL, Ninomiya Y, Mosinger B, Shirazi-Beechey SP.
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15075-80. Epub 2007 Aug 27.

"Recovery of two independent sweet taste systems during regeneration of the mouse chorda tympani nerve after nerve crush."
Yasumatsu K, Kusuhara Y, Shigemura N, Ninomiya Y.
Eur J Neurosci. 2007 Sep;26(6):1521-9. Epub 2007 Aug 20.

"Coding channels for taste perception: information transmission from taste cells to gustatory nerve fibers."
Yoshida R, Yasumatsu K, Shigemura N, Ninomiya Y.
Arch Histol Cytol. 2006 Dec;69(4):233-42. Review.

"Influence of temperature on taste perception."
Talavera K, Ninomiya Y, Winkel C, Voets T, Nilius B.
Cell Mol Life Sci. 2006 Feb;64(4):377-81.

"Taste responsiveness of fungiform taste cells with action potentials."
Yoshida R, Shigemura N, Sanematsu K, Yasumatsu K, Ishizuka S, Ninomiya Y.
J Neurophysiol. 2006 Dec;96(6):3088-95. Epub 2006 Sep 13.

"Induction of salivary kallikreins by the diet containing a sweet-suppressive peptide, gurmarin, in the rat."
Yamada A, Nakamura Y, Sugita D, Shirosaki S, Ohkuri T, Katsukawa H, Nonaka K, Imoto T, Ninomiya Y.
Biochem Biophys Res Commun. 2006 Jul 28;346(2):386-92. Epub 2006 Jun 5.

"Amiloride inhibition on NaCl responses of the Chorda Tympani nerve in two 129 substrains of mice, 129P3/J and 129X1/SvJ."
Ohkuri T, Yasumatsu K, Shigemura N, Yoshida R, Ninomiya Y.
Chem Senses Jul;31(6):565-72. Epub 2006 May 24.

"Trpm5 null mice respond to bitter, sweet, and umami compounds."
Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Perez CA, Shigemura N, Yoshida R, Mosinger B Jr, Glendinning JI, Ninomiya Y, Margolskee RF.
Chem Senses. 2006 Mar;31(3):253-64. Epub 2006 Jan 25.

"Heat-activation of the taste channel TRPM5 underlies thermal sensitivity to sweet."
Talavera K, Yasumatsu K, Voet T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B.
Nature 2005 Dec 15;438(7070):1022-5

"Expression of amiloride-sensitive epithelial sodium channels in mouse taste cells after chorda tympani nerve crush."
Shigemura N, Islam AA, Sadamitsu C, Yoshida R, Yasumatsu K, Ninomiya Y.
Chem Senses. 2005 Jul;30(6):531-8. Epub 2005 Jul 19.

"Mouse strain differences in Gurmarin-sensitivity of sweet taste responses are not associated with polymorphisms of the sweet receptor gene, Tas1r3."
Sanematsu K, Yasumatsu K, Yoshida R, Shigemura N, Ninomiya Y.
Chem Senses. 2005 Jul;30(6):491-6. Epub 2005 Jun 2.

"Temporal changes in NCAM immunoreactivity during taste cell differentiation and cell lineage relationships in taste buds."
Miura H, Kato H, Kusakabe Y, Ninomiya Y, Hino A.
Chem Senses. 2005 May;30(4):367-75. Epub 2005 Mar 30.

"Signal Transduction of Umami Taste: Insights from Knockout Mice."
Rong M, He W, Yasumatsu K, Kokrashvili Z, Perez CA, Mosinger B, Ninomiya Y, Margolskee RF, Damak S.
Chem Senses. 2005 Jan;30(suppl 1):i33-i34.

"cDNA Microarray Screening for Taste-bud-specific Genes."
Kusakabe Y, Shindo Y, Kim MR, Miura H, Ninomiya Y, Hino A.
Chem Senses. 2005 Jan;30 Suppl 1:i12-i13.

"The role of the dpa locus in mice."
Shigemura, N., Yasumatsu, K., Yoshida, R., Sako, N., Katsukawa, H., Nakashima K., Imoto, T., Ninomiya, Y.
Chem Senses. 2005 Jan;30 Suppl 1:i84-i85.

"Recovery of Salt Taste Responses and PGP 9.5 Immunoreactive Taste Bud Cells during Regeneration of the Mouse Chorda Tympani Nerve."
Yasumatsu K, Shigemura N, Yoshida R, Ninomiya Y.
Chem Senses. 2005 Jan;30 Suppl 1:i62-i63.

"Shh signaling and regulatory gene expression in mouse taste buds."
Miura H, Kato H, Kusakabe Y, Tagami M, Miura-Ohnuma J, Ookura T, Shindo Y, Ninomiya Y, Hino A.
Chem Senses. 2005 Jan;30 Suppl 1:i50-i51.

"Taste Receptor Cells Responding with Action Potentials to Taste Stimuli and their Molecular Expression of Taste Related Genes."
Yoshida R, Sanematsu K, Shigemura N, Yasumatsu K, Ninomiya Y.
Chem Senses. 2005 Jan;30 Suppl 1:i19-i20.

"A Strong Nerve Dependence of Sonic hedgehog Expression in Basal Cells in Mouse Taste Bud and an Autonomous Transcriptional Control of Genes in Differentiated Taste Cells."
Miura H, Kato H, Kusakabe Y, Tagami M, Miura-Ohnuma J, Ninomiya Y, Hino A.
Chem Senses. (2004) Nov;29(9):823-31.

"Umami taste responses are mediated by alpha-transducin and alpha-gustducin."
He W* Yasumatsu K,* Varadarajan V, Yamada A, Lem J, Ninomiya Y, Margolskee RF, Damak S. (* equally contributed)
J Neurosci. (2004) 24(35):7674-80.

"Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structure."
Shigemura N., Ohta R., Kusakabe Y., Miura H., Hino A., Koyano K., Nakashima K., Ninomiya Y.
Endocrinology (2004) 145: 839-847

"Regional expression patterns of taste receptors and gustducin in the mouse tongue."
Kim, M.-R., Kusakabe, Y., Miura, H., Shindo, Y., Ninomiya, Y. and Hino, A.
Biochem. Biophys. Res. Commun.(2003) 312: 500-506

"Detection of sweet and umami in the absence of taste receptor T1r3."
Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Varadarajan V, Zou S, Jiang P, Ninomiya Y. and Margolskee RF.
Science (2003) 301: 850-853

"Recovery of amiloride-sensitive neural coding during regeneration of the gustatory nerve: behavioral-neural correlation of salt taste discrimination."
Yasumatsu K, Katsukawa H, Sasamoto K, and Ninomiya Y.
J. Neurosci.(2003) 23: 4362-4368

"Conditioned taste aversion learning in leptin-receptor-deficient db/db mice."
Ohta R, Shigemura N, Sasamoto K, Koyano K. and Ninomiya Y.
Neurobiol. Learn Mem.(2003) 80: 105-112

"Gurmarin suppression of licking responses to sweetener-quinine mixtures in C57BL mice."
Murata Y, Nakashima K, Yamada A, Shigemura N, Sasamoto K, and Ninomiya Y.
Chem. Senses(2003) 28: 237-243

"Co-expression pattern of Shh with Prox1 and that of Nkx2.2 with Mash1 in mouse taste bud."
Miura, H., Kusakabe, Y., Kato, H., Miura-Ohnuma, J., Tagami, M., Ninomiya, Y. and Hino, A.
Gene Expr Patterns.(2003) 3: 427-433

"Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds."
Shigemura N, Miura H, Kusakabe Y, Hino A. and Ninomiya Y.
Arch. Histol. Cytol.(2003) 66: 253-260

"Neural activities in the substantia nigra modulated by stimulation of the orofacial motor cortex and rhythmical jaw movements in the rat."
Nishimuta, K., Sasamoto , K. and Ninomiya, Y.
Neuroscience(2002) 113: 915〜923

"Ion channels and second mesengers involved in transduction and modulation of sweet taste In mouse taste cells. Participation in the suppressive modulation of sweet sensitivity by leptin."
Sugimoto, K., Shigemura, N., Yasumatsu, K., Ohta, R., Nakashima, K., and Ninomiya Y.
Pure Appl. Chem.(2002) 74: 1141-1151

"The discovery of umami."
Lindemann B, Ogiwara Y, Ninomiya Y.
Chem Senses. (2002) Nov;27(9):843-4.

細胞工学 「味を感じる:神経メカニズム」vol.21, 12, 1429-33

"The neural differentiation gene Mash-1 has a distinct pattern of expression from the taste reception-related genes gustducin and T1R2 in the taste buds."
Kusakabe Y, Miura H, Hashimoto R, Sugiyama C, Ninomiya Y, Hino A.
Chem Senses. (2002) Jun;27(5):445-51.

"Leptin and sweet taste."
Ninomiya, Y., Shigemura, N., Ohta, R., Yasumatsu, K., Sugimoto, K., Nakashima, K. and Lindemann, B.
Vitam. Horm.,(2002) 64: 221- 248 (Review)

"Salivary cystatins influence ingestion of capsaicin-containing diets in the rat."
Katsukawa, H., Y. Shang, K. Nakashima, K.H. Yang, R. Ohashi, D. Sugita, K. Mishima, M. Nakata, Y. Ninomiya, T. Sugimura
Life Sci. (2002) 71: 457〜467

"Shh and Ptc are associated with taste bud maintenance in the adult mouse."
Miura H, Kusakabe Y, Sugiyama C, Kawamatsu M, Ninomiya Y, Motoyama J. & Hino A
Mech. Dev. (2001), 106: 143-145

"Molecular genetic identification of a candidate receptor gene for sweet taste."
Kitagawa M, Kusakabe Y, Miura H, Ninomiya Y, & Hino A.
BBRC (2001), 283: 236-242

"Beta-cyclodextrin inhibits the sweet taste suppressing activity of gurmarin by the formation of an inclusion complex with aromatic residues in gurmarin."
Imoto T, Sasamoto K, Ninomiya Y.
Can J Physiol Pharmacol. (2001) Oct;79(10):836-40.

"A comparative study of three cranial sensory ganglia projecting into the oral cavity: in situ hybridization analyses of neurotrophin receptors and thermosensitive cation channels."
Matsumoto I, Emori Y, Ninomiya Y, Abe K.
Brain Res Mol Brain Res. (2001) Sep 30;93(2):105-12.

解き明かされる味覚の情報伝達(訳) 日経サイエンス(2001)6: 54-62

  "Behavioral taste similarities and differences among monosodium L-glutamate and glutamate receptor agonists in C57BL mice."
Nakashima K, Katsukawa H, Sasamoto K, Ninomiya Y.
J Nutr Sci Vitaminol (Tokyo). (2001) Apr;47(2):161-6.

"Analysis of rhythmical jaw movements produced by taste stimulation in rats."
Sasamoto K, Nishimuta K, Yasumatsu K, Ninomiya Y.
J Nutr Sci Vitaminol (Tokyo). (2001) Apr;47(2):156-60

"High-resolution genetic mapping of the saccharin preference locus (Sac) and the putative sweet taste receptor (T1R1) gene (Gpr70) to mouse distal Chromosome 4."
Li X, Inoue M, Reed DR, Huque T, Puchalski RB, Tordoff MG, Ninomiya Y, Beauchamp GK, Bachmanov AA.
Mamm Genome. (2001) Jan;12(1):13-6

"Leptin as a modulator of sweet taste sensitivities in mice."
Kawai, K., Sugimoto, K., Nakashima, K., Miura, H. and Ninomiya, Y.
Proc. Natl. Acad. Sci. USA, (2000) 97: 11044-11049

"Responses to umami substances in taste bud cells innervated by the chorda tympani and glossopharyngeal nerves."
Ninomiya Y, Nakashima K, Fukuda A, Nishino H, Sugimura T, Hino A, Danilova V, & Hellekant G
J. Nutr. (2000), 130: 950S-953S

"Blocking taste receptor activation of gustducin inhibits gustatory responses to bitter compounds."
Ming, D., Ninomiya, Y. and Margolskee, R.F.
Proc. Natl. Acad. Sci. USA, (1999) 97: 9903-9908                   

"Sweet taste responses of mouse chorda tympani neurons: existence of gurmarin-sensitive and -insensitive receptor components."
Ninomiya, Y., Imoto, T. and Sugimura, T.
J. Neurophysiol., (1999) 81: 3087-3091         

"Capsaicin induces cystatin-S-like substances in submandibular saliva of the rat."
Katsukawa, H. and Ninomiya, Y.
J. Dent. Res., (1999) 78: 1609-1616   

"The transduction for sweet taste of saccharin may involve both inositol 1,4,5-triphosphate and cAMP pathways in the fungiform taste buds in C57BL mice."
Nakashima, K. and Ninomiya, Y.
Cell. Physiol. Biochem., (1999) 9: 90-98     

"Induction of salivary gurmarin-binding proteins in rats fed gymnema containing diets."
Katsukawa, H., Imoto, T. and Ninomiya, Y
Chem. Senses, (1999) 24: 387-392

"Modification of behavioral and neural taste responses to NaCl in C57BL/6 mice: effects of NaCl exposure and DOCA treatment."
Bachmanov AA, Inoue M, Tordoff MG, Ninomiya Y, Beauchamp GK.
Physiol Behav. (1999) Jan 1-15;65(4-5):817-22

"Taste in chimpanzees. III: Labeled-line coding in sweet taste."
Hellekant G, Ninomiya Y, Danilova V.
Physiol Behav. 1998 Nov 15;65(2):191-200.                        

"Increase in inositol 1,4,5-triphosphate levels of the fungiform papilla in response to saccharin and bitter substances in mice."
Nakashima, K. and Ninomiya, Y
Cell. Physiol. Biochem., (1998) 8: 224-230             

"Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the diabetic db/db mice."
Ninomiya, Y., Imoto, T., Yatabe, A., Kawamura, S., Nakashima, K. and Katsukawa, H.
Am. J. Physiol., (1998) 274: R1324-R1330 

"Reinnervation of cross-regenerated gustatory nerve fibers into amiloride-sensitive and amiloride-insensitive taste receptor cells."
Ninomiya, Y.
Proc. Natl. Acad. Sci. USA, (1998) 95: 5347-5350               

"Reduction of the suppressive effects of gurmarin on sweet taste responses by addition of β-cyclodextrin."
Ninomiya, Y., Inoue, M. and Imoto, T.
Chem. Senses, (1998) 23: 303-307                       

"NaCl-prefering NZB/B1NJ mice and NaCl-avoiding CBA/J mice have similar amiloride inhibition of chorda tympani responses to NaCl."
Ninomiya, Y., Bachmanov, A.A., Yatabe, A. and Beauchamp, G.K.
Chem. Senses, (1998) 23: 411-416