Research Results|柳沢・船戸研究室|国際統合睡眠医科学研究機構 (WPI-IIIS)|筑波大学

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Journal Articles

  • Nagase H, Yamamoto N, Yata M, Ohrui S, Okada T, Saitoh T, Kutsumura N, Nagumo Y, Irukayama-Tomobe Y, Ishikawa Y, Ogawa Y, Hirayama S, Kuroda D, Watanabe Y, Gouda H, Yanagisawa M. Design and Synthesis of Potent and Highly Selective Orexin 1 Receptor Antagonists with a Morphinan Skeleton and Their Pharmacologies.J Med Chem. 2017 Feb 9;60(3):1018-1040.
  • Ogawa Y, Irukayama-Tomobe Y, Murakoshi N, Kiyama M, Ishikawa Y, Hosokawa N, Tominaga H, Uchida S, Kimura S, Kanuka M, Morita M, Hamada M, Takahashi S, Hayashi Y, Yanagisawa M. Peripherally administered orexin improves survival of mice with endotoxin shock. Elife. 2016 Dec 30;5. pii: e21055.
  • Funato H, Miyoshi C, Fujiyama T, Kanda T, Sato M, Wang Z, Ma J, Nakane S, Tomita J, Ikkyu A, Kakizaki M, Hotta-Hirashima N, Kanno S, Komiya H, Asano F, Honda T, Kim SJ, Harano K, Muramoto H, Yonezawa T, Mizuno S, Miyazaki S, Connor L, Kumar V, Miura I, Suzuki T, Watanabe A, Abe M, Sugiyama F, Takahashi S, Sakimura K, Hayashi Y, Liu Q, Kume K, Wakana S, Takahashi JS, Yanagisawa M. Forward-genetics analysis of sleep in randomly mutagenized mice. Nature. Nov 17;539(7629):378-383.
  • Tsuneki H, Kon K, Ito H, Yamazaki M, Takahara S, Toyooka N, Ishii Y, Sasahara M, Wada T, Yanagisawa M, Sakurai T, Sasaoka T. Timed Inhibition of Orexin System by Suvorexant Improved Sleep and Glucose Metabolism in Type 2 Diabetic db/db Mice. Endocrinology. 2016 Nov;157(11):4146-4157.
  • Hossain MS, Asano F, Fujiyama T, Miyoshi C, Sato M, Ikkyu A, Kanno S, Hotta N, Kakizaki M, Honda T, Kim SJ, Komiya H, Miura I, Suzuki T, Kobayashi K, Kaneda H, Kumar V, Takahashi JS, Wakana S, Funato H, Yanagisawa M. Identification of mutations through dominant screening for obesity using C57BL/6 substrains. Sci Rep. 2016 Sep 2;6:32453.
  • Motoike T, Long JM, Tanaka H, Sinton CM, Skach A, Williams SC, Hammer RE, Sakurai T, Yanagisawa M. Mesolimbic neuropeptide W coordinates stress responses under novel environments. Proc Natl Acad Sci U S A. 2016 May 24;113(21):6023-8.
  • Nagahara T, Saitoh T, Kutsumura N, Irukayama-Tomobe Y, Ogawa Y, Kuroda D, Gouda H, Kumagai H, Fujii H, Yanagisawa M, Nagase H. Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists. J Med Chem. 2015 Oct 22;58(20):7931-7.
  • Lee, I.T., Chang, A.S., Manandhar, M., Shan, Y., Fan, J., Izumo, M., Ikeda, Y., Motoike, T., Dixon, S., Seinfeld, J.E., Takahashi, J.S., Yanagisawa, M. Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms. Neuron. 2015 Mar 4; 85 (5): 1086-102.
  • Tsuneki, H., Tokai, E., Nakamura, Y., Takahashi, K., Fujita, M., Asaoka, T., Kon, K., Anzawa, Y., Wada, T., Takasaki, I., Kimura, K., Inoue, H., Yanagisawa, M., Sakurai, T., Sasaoka, T. Hypothalamic orexin prevents hepatic insulin resistance via daily bidirectional regulation of autonomic nervous system in mice. Diabetes. 2015 Feb; 64 (2): 459-70.
  • Matsuki, T., Takasu, M., Hirose, Y., Murakoshi, N., Sinton, C.M., Motoike, T., Yanagisawa M. GABAA receptor-mediated input change on orexin neurons following sleep deprivation in mice. Neuroscience. 2015 Jan 22; 284: 217-24.
  • Roh, J.H., Jiang, H., Finn, M.B., Stewart, F.R., Mahan, T.E., Cirrito, J.R., Heda, A., Snider, B.J., Li, M., Yanagisawa, M., de Lecea, L., Holtzman, D.M. Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer's disease. J Exp Med. 2014 Dec 15; 211 (13): 2487-96.
  • Emoto, N., Kasuya, Y., Yanagisawa, M. The Second Tomoh Masaki Award (2013). Life Sci. 2014 Nov 24; 118 (2): 87-90.
  • Emoto, N., Vignon-Zellweger, N., Lopes, R.A., Cacioppo, J., Desbiens, L., Kamato, D., Leurgans, T., Moorhouse, R., Straube, J., Wurm, R., Heiden, S., Ergul, A., Yanagisawa, M., Barton, M. 25 years of endothelin research: the next generation. Life Sci. 2014 Nov 24; 118 (2): 77-86.
  • Emoto, N., Yanagisawa, M. The Thirteenth International Conference on Endothelin (ET-13), Tokyo, 2013. Life Sci. 2014 Nov 24; 118 (2): 70-6.
  • Wang, Z., Liu, S., Kakizaki, M., Hirose, Y., Ishikawa, Y., Funato, H., Yanagisawa, M., Yu, Y., Liu, Q. Orexin/hypocretin activates mTOR complex 1 (mTORC1) via an Erk/Akt-independent and calcium-stimulated lysosome v-ATPase pathway. J Biol Chem. 2014 Nov 14; 289 (46): 31950-9.
  • Mohammed, M., Ootsuka, Y., Yanagisawa, M., & Blessing, W. Reduced brown adipose tissue thermogenesis during environmental interactions in transgenic rats with ataxin-3-mediated ablation of hypothalamic orexin neurons. Am J Physiol Regul Integr Comp Physiol. 2014 Oct 15; 307 (8): R978-89.
  • Lehmann, L.H., Rostosky, J.S., Buss, S.J., Kreusser, M.M., Krebs, J., Mier. W., Enseleit, F., Spiger, K., Hardt, S.E., Wieland, T., Haass, M., Lüscher, T.F., Schneider, M.D., Parlato, R., Gröne, H.J., Haberkorn, U., Yanagisawa, M., Katus, H.A., Backs, J. Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling. Proc Natl Acad Sci U S A. 2014 Sep 16; 111 (37): 13499-504.
  • Oda, S., Funato, H., Sato, F., Adachi-Akahane, S., Ito, M., Takase, K., & Kuroda, M. A subset of thalamocortical projections to the retrosplenial cortex possesses two vesicular glutamate transporter isoforms, VGluT1 and VGluT2, in axon terminals and somata. J Comp Neurol. 2014 Jun 15; 522 (9): 2089-106.
  • Takase, K., Kikuchi, K., Tsuneoka, Y., Oda, S., Kuroda, M., & Funato, H. Meta-analysis of melanin-concentrating hormone signaling-deficient mice on behavioral and metabolic phenotypes. PLoS One. 2014 Jun 12; 9 (6): e99961.
  • Wei, W., Motoike, T., Krzeszinski, J.Y., Jin, Z., Xie, X.J., Dechow, P.C., Yanagisawa, M., & Wan, Y. Orexin Regulates Bone Remodeling via a Dominant Positive Central Action and a Subordinate Negative Peripheral Action. Cell Metab. 2014 Jun 3; 19 (6): 927-40.
  • Makino, K., Jinnin, M., Aoi, J., Kajihara, I., Makino, T., Fukushima, S., Sakai, K., Nakayama, K., Emoto, N., Yanagisawa, M., & Ihn, H. Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing. PLoS One. 2014 May 22; 9 (5): e97972.
  • Cacioppo, J.A., Oh, S.W., Kim, H.Y., Cho, J., Lin, P.C., Yanagisawa, M., & Ko, C. Loss of function of endothelin-2 leads to reduced ovulation and CL formation. PLoS One. 2014 Apr 24; 9 (4): e96115.
  • Heiden, S., Vignon-Zellweger, N., Masuda, S., Yagi, K., Nakayama, K., Yanagisawa, M., & Emoto, N. Vascular endothelium derived endothelin-1 is required for normal heart function after chronic pressure overload in mice. PLoS One. 2014 Feb 11; 9 (2): e88730.
  • Kohlmeier, K.A., Tyler, C.J., Kalogiannis, M., Ishibashi, M., Kristensen, M.P., Gumenchuk, I., Chemelli, R.M., Kisanuki, Y., Yanagisawa, M., Leonard, C.S. Differential actions of orexin receptors in brainstem cholinergic and monoaminergic neurons revealed by receptor knockouts: implications for orexinergic signaling in arousal and narcolepsy. Front Neurosci. 2013 Dec 20; 7: 246.
  • Ikeda, Y., Kumagai, H., Skach, A., Sato, M., Yanagisawa, M. Modulation of circadian glucocorticoid oscillation via adrenal opioid-CXR7 signaling alters emotional behavior. Cell. 2013 Dec 5; 155 (6): 1323-36.
  • Hasegawa, E., Yanagisawa, M., Sakurai, T. & Mieda, M. Orexin neurons suppress narcolepsy via 2 distinct efferent pathways. J Clin Invest. 2014 Feb 3; 124 (2): 604-16.
  • Soya, S., Shoji, H., Hasegawa, E., Hondo, M., Miyakawa, T., Yanagisawa, M., Mieda, & M., Sakurai, T. Orexin receptor-1 in the locus coeruleus plays an important role in cue-dependent fear memory consolidation. J Neurosci. 2013 Sep 4; 33 (36): 14549-57.
  • Furutani, N., Hondo, M., Kageyama, H., Tsujino, N., Mieda, M., Yanagisawa, M., Shioda, S., & Sakurai, T. Neurotensin co-expressed in orexin-producing neurons in the lateral hypothalamus plays an important role in regulation of sleep/wakefulness states. PLoS One. 2013 Apr 19; 8 (4): e62391.
  • Suzuki, A, Sinton CM, Greene RW, & Yanagisawa M. Behavioral and biochemical dissociation of arousal and homeostatic sleep need influenced by prior wakeful experience in mice. Proc Natl Acad Sci U S A. 2013 Jun 18; 110 (25): 10288-10293.
  • Chang, I., Bramall, A.N,, Baynash, A.G., Rattner, A., Rakheja, D., Post, M., Joza, S., McKerlie, C., Stewart, D.J., McInnes, R.R., & Yanagisawa, M. Endothelin-2 deficiency causes growth retardation, hypothermia, and emphysema in mice. J Clin Invest. 2013 Jun 3; 123 (6): 2643-53.
  • Takase, K., Oda, S., Kuroda, M., & Funato, H. Monoaminergic and neuropeptidergic neurons have distinct expression profiles of histone deacetylases. PLoS One. 2013; 8 (3): e58473.
  • Mieda, M., Hasegawa, E., Kisanuki, Y.Y., Sinton, C.M., Yanagisawa, M., & Sakurai, T. Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. J Neurosc. 2011 Apr 27; 31 (17): 6518-26.
  • Funato, H., Sato, M., Sinton, C.M., Gautron, L., Williams, S.C., Skach, A., Elmquist, J.K., Skoultchi, A.I., & Yanagisawa, M. Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep. Proc Natl Acad Sci U S A. 2010 Oct 19; 107 (42): 18155-60.
  • Matsuki, T., Nomiyama, M., Takahira, H., Hirashima. N., Kunita, S., Takahashi, S., Yagami, K., Kilduff, T.S., Bettler, B., Yanagisawa, M. & Sakurai, T. Selective loss of GABA(B) receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture. Proc Natl Acad Sci U S A. 2009 Mar 17; 106 (11): 4459-64.
  • Irukayama-Tomobe, Y., Tanaka, H., Yokomizo, T., Yanagisawa, M. & Sakurai, T. Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B. Proc Natl Acad Sci U S A. 2009 Mar 10; 106 (10): 3930-4.
  • Sakakibara, I., Fujino, T., Ishii, M., Tanaka, T., Shimosawa, T., Miura, S., Zhang, W., Tokutake, Y., Yamamoto, J., Awano, M., Iwasaki, S., Motoike, T., Okamura, M., Inagaki, T., Kita, K., Ezaki, O., Naito, M., Kuwaki, T., Chohnan, S., Yamamoto, T., Hammer, R.E., Kodama, T., Yanagisawa, M., & Sakai, J. Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2. Cell Metab. 2009 Feb; 9 (2): 191-202.
  • Funato, H., Tsai, A.L., Willie, J.T., Kisanuki Y., Williams, S.C., Sakurai, T., & Yanagisawa, M. Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metab. 2009 Jan 7; 9 (1): 64-76.
  • Mieda, M., Williams, S.C., Richardson, J.A., Tanaka, K. & Yanagisawa, M. The dorsomedial hypothalamic nucleus as a putative food-entrainable circadian pacemaker. Proc Natl Acad Sci U S A. 2006 Aug 8; 103 (32): 12150–5.
  • Takayasu, S., Sakurai, T., Iwasaki, S., Teranishi, H., Yamanaka, A., Williams, S.C., Iguchi, H., Kawawawa, Y.I., Ikeda, Y., Sakakibara, I. Ohno, K. Ioka, R.X., Murakami, S., Dohmae, N., Xie, J., Suda, T., Motoike, T. Ohuchi, T., Yanagisawa, M. & Saka, J. A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice. Proc Natl Acad Sci U S A. 2006 May 9; 103 (19): 7438-43.
  • Sakurai, T., Nagata, R., Yamanaka, A., Kawamura, H., Tsujino, N., Muraki, Y., Kageyama, H., Kunita, S., Takahashi, S., Goto, K., Koyama, Y., Shioda, S. & Yanagisawa, M. Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron. 2005 Apr 21: 46 (2): 297–308.
  • Mieda, M., Williams, S.C., Sinton, C.M., Richardson, J.A., Sakurai, T. & Yanagisawa, M. Orexin neurons function in an efferent pathway of a food-entrainable circadian oscillator in eliciting food-anticipatory activity and wakefulness. J Neurosci. 2004 Nov 17; 24 (46): 10493-501.
  • Mieda, M., Willie, J.T., Hara, J., Sinton, C.M., Sakurai, T. & Yanagisawa, M. Orexin peptides prevent cataplexy and improve wakefulness in orexin neuron-ablated model of narcolepsy in mice. Proc Natl Acad Sci U S A. 2004 Mar 30; 101 (13): 4649-54.
  • Beuckmann, C.T., Sinton, C.M., Williams, S.C., Richardson, J.A. Hammer, R.E., Sakurai, T. & Yanagisawa, M. Expression of a poly-glutamine-ataxin-3 transgene in orexin neurons induces narcolepsy-cataplexy in the rat. J Neurosci. 2004 May 5; 24 (18): 4469-77.
  • Xiong, Y., Miyamoto, N., Shibata, K., Valasek, M.A., Motoike, T., Kedzierski, R.M., & Yanagisawa, M. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci U S A. 2004 Jan 27; 101 (4): 1045-50.
  • Willie, J.T., Chemelli, R.M., Sinton, C.M., Tokita, S., Williams, S.C., Kisanuki, Y.Y., Marcus, J.N., Lee, C., Elmquist, J.K., Kohlmeier, K.A., Leonard, C.S., Richardson, J.A., Hammer, R.E. & Yanagisawa, M. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron 2003 Jun 5; 38 (5): 715-30.
  • Yamanaka, A., Beuckmann, C.T., Willie, J.T., Hara, J., Tsujino, N., Mieda, M., Tominaga, M., Yagami, K., Sugiyama, F., Goto, K., Yanagisawa, M. & Sakurai, T. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron. 2003 Jun 5; 38 (5): 701-13.
  • Tanaka, H., Yoshida, T., Miyamoto, N., Motoike, T., Kurosu, H., Shibata, K., Yamanaka, A., Williams, S.C., Richardson, J.A., Tsujino, N., Garry, M.G., Lerner, M.R., King, D.S., O’Dowd, B.F., Sakurai, T. & Yanagisawa, M. Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. Proc Natl Acad Sci U S A. 2003 May 13; 100 (10): 6251-6.
  • Okazaki, Y. & FANTOM Consortium, RIKEN Genome Exploration Research Group Phase I & II Team. Analysis of the mouse transcriptome based on functional annotation of 60,770 full length cDNAs. Nature. 2002 Dec 5; 420 (6915): 563-73.
  • Hara, J., Beuckmann, C. T., Nambu, T., Willie, J. T., Chemelli, R. M., Sinton, C. M., Sugiyama, F., Yagami, K., Goto, K. Yanagisawa, M. & Sakurai, T. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron. 2001 May; 30 (2): 345-54.
  • Kedzierski, R. M. & Yanagisawa, M. Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol. 2001; 41: 851–76.
  • Willie, J. T., Chemelli, R. M., Sinton, C. M., & Yanagisawa, M. To eat or sleep? Orexin in the regulation of feeding and wakefulness. Annu Rev Neurosci Toxicol. 2001 Mar; 24: 429–458.
  • Gariepy, C. G., Ohuchi, T., Williams, S. C., Richardson, J. A. & Yanagisawa, M. Salt-sensitive hypertension in endothelin-B receptor-deficient rats. J Clin Invest. 2000 Apr; 105 (7): 925-333.
  • Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y., Kisanuki, Y., Fitch, T. E., Nakazato, M., Hammer, R. E., Saper, C. B. & Yanagisawa, M. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999 Aug 20; 98 (4): 437-51.
  • Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., Williams, S. C., Richardson, J. A., Kozlowski, G. P., Wilson, S., Arch, J. R. S., Buckingham, R. E., Haynes, A. C., Carr, S. A., Annan, R. S., McNulty, D. E., Liu, W.-S., Terrett, J. A., Elshourbagy, N. A., Bergsma, D. J. & Yanagisawa, M. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998 Feb 20; 92 (4): 573-85.
  • Yanagisawa, H., Yanagisawa, M., Kapur, R. P., Richardson, J. A., Williams, S. C., Clouthier, D. E., de Wit, D., Emoto, N. & Hammer, R. E. Dual genetic pathways of endothelin-mediated intercellular signaling revealed by targeted disruption of endothelin converting enzyme-1 gene. Development. 1998 Mar; 125 (5): 825-36.
  • Puffenberger, E. G., Hosoda, K., Washington, S. S., Nakao, K., deWit, D., Yanagisawa, M. & Chakravarti, A. A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung’s disease. Cell. 1994 Dec 30; 79 (7): 1257-66.
  • Baynash, A. G., Hosoda, K., Giaid, A., Richardson, J. A., Emoto, N., Hammer, R. E. & Yanagisawa, M. Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell. 1994 Dec 30; 79 (7): 1277-85.
  • Hosoda, K., Hammer, R. E., Richardson, J. A., Greenstein Baynash, A., Cheung, J. C., Giaid, A. & Yanagisawa, M. Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell. 1994 Dec 30; 79 (7): 1267-76.
  • Xu, D., Emoto, N., Giaid, A., Slaughter, C., Kaw, S., deWit, D. & Yanagisawa, M. ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1. Cell. 1994 Aug 12; 78 (3): 473-85.
  • Sakurai, T., Yanagisawa, M., Takuwa, Y., Miyazaki, H., Kimura, S., Goto, K. & Masaki, T. Cloning of a cDNA encoding a non-isopeptide selective subtype of the endothelin receptor. Nature. 1990 Dec 20-27; 348 (6303): 732-5.
  • Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K. & Masaki, T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31; 332 (6163): 411-5.

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