Studies on the biological regulatory mechanisms by a novel bioactive peptide, neuromedin U precursor-related peptide (NURP)

• Project/Area Number: 18K08497
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: MORI Kenji 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (00416223)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 生理活性ペプチド / 神経ペプチド / 受容体

Outline of Final Research Achievements

To understand the role of neuromedin U precursor-related peptide (NURP), which has potent prolactin-releasing activity, the mechanism of biological regulation by this peptide was examined.
Although neuromedin U (NMU), produced from the same precursor protein as NURP, inversely inhibits prolactin secretion, NURP could not function as an antagonist of the NMU receptors, suggesting that it induces prolactin release through specific receptor for NURP. In addition, in rat brain, intracerebroventricular administration of NURP activated neurons in the hypothalamic arcuate nucleus without activating dopaminergic neurons, which inhibit prolactin secretion from the anterior pituitary. In addition, specific neuronal activation was observed in the ventral subiculum. These data suggest the presence of NURP receptors in the activated region of the rat brain.

Academic Significance and Societal Importance of the Research Achievements

新しく発見した強力なプロラクチン分泌促進活性を持つ生理活性ペプチドであるNURPについて、その作用機序と脳室内投与によって活性化される神経細胞を検討した結果、NURP受容体を同定するための基礎的情報を得るとともに、本ペプチドの新たな機能の存在を示唆した。これまで、生理活性ペプチドとその受容体は、創薬研究の重要な標的とされてきたことから、本研究の進展により応用研究への発展が期待できる。

Research Products

• [Journal Article] Comparison of physiological functions between neuromedin U-related peptide and neuromedin S-related peptide in the rat central nervous system (2021)
  • Author(s): Tanaka Yukie、Taguchi Shimon、Maruyama Keisuke、Mori Kenji、Miyazato Mikiya、Kangawa Kenji、Murakami Noboru、Nakahara Keiko
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 534 Pages: 653-658
  • DOI: 10.1016/j.bbrc.2020.11.025
  • Peer Reviewed / Open Access
• [Journal Article] A chemically stable peptide agonist to neuromedin U receptor type 2 (2020)
  • Author(s): Takayama Kentaro、Mori Kenji、Tanaka Akiko、Sasaki Yu、Sohma Yuko、Taguchi Akihiro、Taniguchi Atsuhiko、Sakane Toshiyasu、Yamamoto Akira、Miyazato Mikiya、Minamino Naoto、Kangawa Kenji、Hayashi Yoshio
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 28 Issue: 10 Pages: 115454-115454
  • DOI: 10.1016/j.bmc.2020.115454
  • Peer Reviewed
• [Journal Article] Cocaine has some effect on neuromedin U expressing neurons related to the brain reward system (2020)
  • Author(s): Anan Madoka、Higa Ryoko、Shikano Kenshiro、Shide Masahito、Soda Akinobu、Carrasco Apolinario Magdeline E.、Mori Kenji、Shin Toshitaka、Miyazato Mikiya、Mimata Hiromitsu、Hikida Takatoshi、Hanada Toshikatsu、Nakao Kazuwa、Kangawa Kenji、Hanada Reiko
  • Journal Title: Heliyon Volume: 6 Issue: 5 Pages: e03947-e03947
  • DOI: 10.1016/j.heliyon.2020.e03947
  • Peer Reviewed / Open Access
• [Journal Article] Design and synthesis of peptidic partial agonists of human neuromedin U receptor 1 with enhanced serum stability (2020)
  • Author(s): Takayama Kentaro、Mori Kenji、Asari Tomo、Sohma Yuko、Nomura Erina、Sasaki Yu、Taguchi Akihiro、Taniguchi Atsuhiko、Miyazato Mikiya、Minamino Naoto、Kangawa Kenji、Hayashi Yoshio
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 30 Issue: 18 Pages: 127436-127436
  • DOI: 10.1016/j.bmcl.2020.127436
  • Peer Reviewed
• [Journal Article] Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode (2020)
  • Author(s): Shiimura Yuki、Horita Shoichiro、Hamamoto Akie、Asada Hidetsugu、Hirata Kunio、Tanaka Misuzu、Mori Kenji、Uemura Tomoko、Kobayashi Takuya、Iwata So、Kojima Masayasu
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41467-020-17554-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transnasal delivery of the peptide agonist specific to neuromedin-U receptor 2 to the brain for the treatment of obesity. (2020)
  • Author(s): 3.Tanaka A, Takayama K, Furubayashi T, Mori K, Takemura Y, Amano M, Maeda C, Inoue D, Kimura S, Kiriyama A, Katsumi H, Miyazato M, Kangawa K, Sakane T, Hayashi Y, and Yamamoto A
  • Journal Title: Mol. Pharm. Volume: 17 Issue: 1 Pages: 32-39
  • DOI: 10.1021/acs.molpharmaceut.9b00571
  • Peer Reviewed / Open Access
• [Journal Article] Neuromedin U suppresses prolactin secretion via dopamine neurons of the arcuate nucleus. (2020)
  • Author(s): 2.Nakahara K, Maruyama K, Ensho T, Mori K, Miyazato M, Kangawa K, Uemura R, Sakota H, Nakazato M, and Murakami N
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 521 Issue: 2 Pages: 521-526
  • DOI: 10.1016/j.bbrc.2019.10.156
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a novel neuropeptide with prolactin-releasing activity (2019)
  • Author(s): 森健二
  • Journal Title: 生化学 Volume: 91 Issue: 5 Pages: 697-700
  • DOI: 10.14952/SEIKAGAKU.2019.910697
  • NAID: 40022059269
  • ISSN: 0037-1017
  • Year and Date: 2019-10-25
• [Presentation] 8.新規生理活性ペプチドであるNeuromedin U precursor-related peptideの同定とその機能 (2019)
  • Author(s): 森健二，宮里幹也，寒川賢治
  • Organizer: 日本薬学会第139年会
• [Presentation] 1.新規生理活性ペプチドneuromedin U precursor-related peptide (NURP)の発見とそのプロラクチン分泌促進活性 (2018)
  • Author(s): 森健二，井田隆徳，中原桂子，村上昇，宮里幹也，寒川賢治
  • Organizer: 第91回日本内分泌学会学術総会