Studies on comprehensive physiological functions of novel exogenous neuromodulating peptides

• Project/Area Number: 23380076
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: Kyoto University
• Principal Investigator: OHINATA Kousaku 京都大学, (連合)農学研究科(研究院), 准教授 (00361147)
• Co-Investigator(Renkei-kenkyūsha): URADE Yoshihiro 大阪バイオサイエンス研究所, 研究部長 (10201360)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2013: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2011: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: ペプチド / 情動調節 / 睡眠 / 食欲 / エネルギー代謝 / 摂食 / 脳・神経 / 抗不安作用 / 中枢神経系 / ジペプチド

Research Abstract

We investigated interaction between low-molecular weight peptides and the nervous system. We found novel anxiolytic-like peptides released from food proteins by gastrointestinal proteases, based on structure-activity relationship of potent anxiolytic peptides. The food-derived peptides may be one of exogenous neuromodulating factors. We also found that low-molecular peptides with neuromodulating activities sometimes exhibited sleep inducting activity, changed food intake, and modulated energy metabolism.

Research Products

• [Journal Article] δ-Opioid receptor activation stimulates normal diet intake but conversely suppresses high-fat diet intake in mice (2014)
  • Author(s): Kaneko K, Mizushige T, Miyazaki Y, Lazarus M, Urade Y, Yoshikawa M, Kanamoto R, Ohinata K
  • Journal Title: Am J Physiol Regul Integr Comp Physiol Volume: 306(4)
  • Peer Reviewed
• [Journal Article] Characterization of Ile-His-Arg-Phe, a novel rice-derived vasorelaxing peptide with hypotensive and anorexigenic activities (2014)
  • Author(s): Kontani N, Omae R, Kagebayashi T, Kaneko K, Yamada Y, Mizushige T, Kanamoto R, Ohinata K
  • Journal Title: Mol Nutr Food Res Volume: 58(2) Pages: 359-64
  • Peer Reviewed
• [Journal Article] Identification of novel β-lactoglobulinderived peptides, wheylin-1 and -2, having anxiolytic-like activity in mice (2014)
  • Author(s): Yamada A, Mizushige T, Kanamoto R, Ohinata K
  • Journal Title: Mol Nutr Food Res Volume: 58(2) Pages: 353-8
  • Peer Reviewed
• [Journal Article] δ-Opioid receptor activation stimulates normal diet intake but conversely suppresses high-fat diet intake in mice. (2014)
  • Author(s): Kaneko K, Mizushige T, Miyazaki Y, Lazarus M, Urade Y, Yoshikawa M, Kanamoto R, Ohinata K.
  • Journal Title: Am J Physiol Regul Integr Comp Physiol. Volume: 306(4) Issue: 4 Pages: 265-272
  • DOI: 10.1152/ajpregu.00405.2013
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of Ile-His-Arg-Phe, a novel rice-derived vasorelaxing peptide with hypotensive and anorexigenic activities. (2014)
  • Author(s): Kontani N, Omae R, Kagebayashi T, Kaneko K, Yamada Y, Mizushige T, Kanamoto R, Ohinata K.
  • Journal Title: Mol Nutr Food Res. Volume: 58(2) Issue: 2 Pages: 359-64
  • DOI: 10.1002/mnfr.201300334
  • Peer Reviewed
• [Journal Article] Identification of novel β-lactoglobulin-derived peptides, wheylin-1 and -2, having anxiolytic-like activity in mice. (2014)
  • Author(s): Yamada A, Mizushige T, Kanamoto R, Ohinata K.
  • Journal Title: Mol Nutr Food Res. Volume: 58(2) Issue: 2 Pages: 353-8
  • DOI: 10.1002/mnfr.201300237
  • Peer Reviewed
• [Journal Article] Characterization of Tyr-Leu-Gly, a novel anxiolytic-like peptide released from bovine αS-casein (2013)
  • Author(s): Mizushige T, Sawashi Y, Yamada A, Kanamoto R, Ohinata K
  • Journal Title: FASEB J Volume: 27(7) Pages: 2911-7
  • Peer Reviewed
• [Journal Article] Aromatic amino acid-leucine dipeptides exhibit anxiolytic-like activity in young mice (2013)
  • Author(s): Mizushige T, Kanegawa N, Yamada A, Ota A, Kanamoto R, Ohinata K
  • Journal Title: Neurosci Lett Volume: 543 Pages: 126-9
  • Peer Reviewed
• [Journal Article] Characterization of Tyr-Leu-Gly, a novel anxiolytic-like peptide released from bovine αS-casein. (2013)
  • Author(s): Mizushige T, Sawashi Y, Yamada A, Kanamoto R, Ohinata K.
  • Journal Title: FASEB J Volume: 27(7) Issue: 7 Pages: 2911-7
  • DOI: 10.1096/fj.12-225474
  • Peer Reviewed
• [Journal Article] Aromatic amino acid-leucine dipeptides exhibit anxiolytic-like activity in young mice. (2013)
  • Author(s): Mizushige T, Kanegawa N, Yamada A, Ota A, Kanamoto R, Ohinata K.
  • Journal Title: Neurosci Lett. Volume: 543 Pages: 126-9
  • DOI: 10.1016/j.neulet.2013.03.043
  • Peer Reviewed
• [Journal Article] Novel orexigenic pathway prostaglandin D2-NPY system--involvement in orally active orexigenic δ opioid peptide (2012)
  • Author(s): Kaneko K, Yoshikawa M, Ohinata K
  • Journal Title: Neuropeptides Volume: 46(6) Pages: 353-7
  • Peer Reviewed
• [Journal Article] Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents (2012)
  • Author(s): Kagebayashi T, Kontani N, Yamada Y, Mizushige T, Arai T, Kino K, Ohinata K.
  • Journal Title: Mol Nutr Food Res Volume: 56(9) Pages: 1456-63
  • Peer Reviewed
• [Journal Article] Orally administered rubiscolin-6, a δ opioid peptide derived from Rubisco, stimulates food intake via leptomeningeal lipocallin-type prostaglandin D synthase in mice (2012)
  • Author(s): Kaneko K, Lazarus M, Miyamoto C, Oishi Y, Nagata N, Yang S, Yoshikawa M, Aritake K, Furuyashiki T, Narumiya S, Urade Y, Ohinata K
  • Journal Title: Mol Nutr Food Res Volume: 56(8) Pages: 1315-23
  • Peer Reviewed
• [Journal Article] Characterization of ovolin, an orally active tryptic peptide released from ovalbumin with anxiolytic-like activity (2012)
  • Author(s): Oda A, Kaneko K, Mizushige T, Lazarus M, Urade Y, Ohinata K
  • Journal Title: J Neurochem Volume: 122(2) Pages: 356-62
  • Peer Reviewed
• [Journal Article] Complement C5a exhibits anxiolytic-like activity via the prostaglandin D_2-DP_1 receptor system coupled to adenosine A_<2A> and GABA_<A> receptors (2012)
  • Author(s): Miyamoto C, Yoshida M, Yoshikawa M, Mizushige T, Ohinata K
  • Journal Title: Prostaglandins Other Lipid Mediat Volume: 98(1-2) Pages: 17-22
  • Peer Reviewed
• [Journal Article] Soymorphin-5, a soy-derived μ-opioid peptide, decreases glucose and triglyceride levels through activating adiponectin and PPARα systems in diabetic KKAy mice (2012)
  • Author(s): Yamada Y, Muraki A, Oie M, Kanegawa N, Oda A, Sawashi Y, Kaneko K, Yoshikawa M, Goto T, Takahashi N, Kawada T, Ohinata K
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 302(4)
  • Peer Reviewed
• [Journal Article] Characterization of ovolin, an orally active tryptic peptide released from ovalbumin with anxiolytic-like activity. (2012)
  • Author(s): Oda A, Kaneko K, Mizushige T, Lazarus M, Urade Y, Ohinata K.
  • Journal Title: J Neurochem. Volume: 122 Issue: 2 Pages: 356-362
  • DOI: 10.1111/j.1471-4159.2012.07777.x
  • Peer Reviewed
• [Journal Article] Orally administered rubiscolin-6, a δ opioid peptide derived from Rubisco, stimulates food intake vialeptomeningeal lipocallin-type prostaglandin D synthase in mice. (2012)
  • Author(s): Kaneko K, Lazarus M, Miyamoto C, Dishi Y, Nagata N, Yang S. Yoshikawa M. Aritake K, Furuyashiki T, Narumiya S, Urade Y, Chinata K.
  • Journal Title: Mol Nutr Food Res. Volume: 56(8) Issue: 8 Pages: 1315-1323
  • DOI: 10.1002/mnfr.201200155
  • Peer Reviewed
• [Journal Article] Novel CCK-dependent vasorelaxing dipeptide, Arg-Phe, decreases blood pressure and food intake in rodents. (2012)
  • Author(s): Kagebayashi T, Kontani N, Yamada Y, Mizushige T, Arai T, Kino K, Ohinata K.
  • Journal Title: Mol Nutr Food Res. Volume: 56(9): Issue: 9 Pages: 1456-63
  • DOI: 10.1002/mnfr.201200168
  • Peer Reviewed
• [Journal Article] Complement C5a exhibits anxiolytic-like activity via the prostaglandin D2-DP1 receptor system coupled to adenosine A2A and GABAA receptors. (2012)
  • Author(s): Miyamoto C, Yoshida M, Yoshikawa M, Mizushige T, Ohinata K.
  • Journal Title: Prostaglandins Other Lipid Mediat. Volume: 98(1-2) Issue: 1-2 Pages: 17-22
  • DOI: 10.1016/j.prostaglandins.2012.03.004
  • Peer Reviewed
• [Journal Article] Novel orexigenic pathway prostaglandin D2-NPY system - involvement in orally active orexigenic δopioid peptide. (2012)
  • Author(s): Kaneko K, Yoshikawa M, Ohinata K.
  • Journal Title: Neuropeptides Volume: 46(6) Issue: 6 Pages: 353-357
  • DOI: 10.1016/j.npep.2012.10.003
  • Peer Reviewed
• [Journal Article] Soymorphin-5, a soy-derived μ-opioid peptide, decreases glucose and triglyceride levels through activating adiponectin and PPAR α systems in (2012)
  • Author(s): Yamada Y, Muraki A, Oie M, Kanegawa N, Oda A, Sawashi Y
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 302
  • Peer Reviewed
• [Journal Article] β-Lactotensin derived from bovine β-lactoglobulin exhibits anxiolytic-like activity as an agonist for neurotensin NTS2 receptor via activation of dopamine D1 receptor in mice (2011)
  • Author(s): Hou IC, Suzuki C, Kanegawa N, Oda A, Yamada A, Yoshikawa M, Yamada D, Sekiguchi M, Wada E, Wada K, Ohinata K
  • Journal Title: J Neurochem Volume: 119(4) Pages: 785-90
  • Peer Reviewed
• [Journal Article] Central PGE_2 exhibits anxiolytic-like activity via EP_1 and EP_4 receptors in a manner dependent on serotonin 5-HT_<1A>, dopamine D_1 and GABA_A receptors (2011)
  • Author(s): Suzuki C, Miyamoto C, Furuyashiki T, Narumiya S, Ohinata K
  • Journal Title: FEBS Lett Volume: 585(14) Pages: 2357-62
  • Peer Reviewed
• [Journal Article] β-lactotensin derived from bovine b-lactoglobulin exhibits a nxiolytic-kike activity as an agonist for neurotensin NTS2 receptor via activation of dopatnine D1 receptor in mice (2011)
  • Author(s): Hou, I.C., et al
  • Journal Title: J Neurochem Volume: 119 Issue: 4 Pages: 785-790
  • DOI: 10.1111/j.1471-4159.2011.07472.x
  • Peer Reviewed
• [Journal Article] Central PGE_2 exhibits anxiolytic-like activity via EP1 and EP4 receptors in a manner dependent on serotonin 5-HT1A, dopamine D1 and GABAA receptors (2011)
  • Author(s): Suzuki, C., Miyamoto, C., Furuyashiki, T., Narumiya, S., Ohinata, K.
  • Journal Title: FEBS Lett. Volume: 585 Issue: 14 Pages: 2357-2362
  • DOI: 10.1016/j.febslet.2011.06.004
  • Peer Reviewed
• [Presentation] Food-derived orexigenic peptide (2013)
  • Author(s): Kousaku Ohinata
  • Organizer: 第7回国際カヘキシアカンファランス種子島シンポジウム
  • Place of Presentation: 種子島
  • Year and Date: 2013-12-13
• [Presentation] 消化管ホルモンを介する外因性ペプチドの多様な生理作用 (2013)
  • Author(s): 大日向耕作
  • Organizer: 第5回アミノ酸学会夏のシンポジウム
  • Place of Presentation: 小樽
  • Year and Date: 2013-07-26
• [Presentation] 神経調節ペプチド (2013)
  • Author(s): 大日向耕作, 水重貴文, 金本龍平
  • Organizer: 日本栄養・食糧学会シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2013-05-26
• [Presentation] Novel orally active peptides derived from food proteins (2012)
  • Author(s): Kousaku Ohinata
  • Organizer: Cornell University-Kyoto University Joint Symposium on Bioactive Food Components
  • Place of Presentation: Cornell Univ., Ithaka, NY, USA
  • Year and Date: 2012-03-05
• [Presentation] Orally Active Neuromodulatory Peptides (2012)
  • Author(s): Kousaku Ohinata
  • Organizer: 103th AOCS Annual Meeting & Expo
  • Place of Presentation: Long Beach, CA, USA
• [Presentation] コメ由来ペプチドの多機能性と持続化作用 (2012)
  • Author(s): 大日向耕作
  • Organizer: 日本栄養・食糧学会シンポジウム
  • Place of Presentation: 仙台
• [Presentation] Orally Active Neuromodulatory Peptides (2012)
  • Author(s): Ohinata Kousaku
  • Organizer: 103ｔｈ AOCS Annual Meeting & Expo
  • Place of Presentation: Long Beach, CA,USA
  • Invited
• [Presentation] コメ由来ペプチドの多機能性と持続化作用 (2012)
  • Author(s): 大日向耕作
  • Organizer: 第66回 日本栄養・食糧学会大会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] PGE_2 はEP_4/EP_1 受容体を介して抗不安作用を示す (2011)
  • Author(s): 大日向耕作
  • Organizer: 日本生化学会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] FGE2はEP1/EF4受容体を介して抗不安作用を示す (2011)
  • Author(s): 大日向耕作
  • Organizer: 日本生化学会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] Novel orally active peptides derived from food proteins
  • Author(s): Ohinata Kousaku
  • Organizer: Cornell University-Kyoto University Joint Symposium on Bioactive Food Components
  • Place of Presentation: Cornell University, Ithaka, NY, USA
  • Invited