Study of molecular basis of motilin and growth hormone secretagogue receptor

• Project/Area Number: 17K09350
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Ehime University
• Principal Investigator: Matsuura Bunzo 愛媛大学, 医学系研究科, 寄附講座教授 (80284420)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: モチリン受容体 / グレリン受容体 / 受容体活性化機構 / 受容体脱感作機構 / トランスジェニックマウス / 脳-消化管連関 / 脳消化管連関 / 受容体相互連関 / ユビキチン

Outline of Final Research Achievements

Motilin, erythromycin and ghrelin are important endogenous regulators of gastrointestinal motor function, mediated by the class A G protein-coupled motilin receptor (MLNR) and growth hormone secretagogue receptor (GHSR). We have clarified pre-stimulation with motilin induces desensitization of MLNR, while that with erythromycin or other macrolides do not. We also have clarified the level of acyl-ghrelin is significantly attenuated by MLNR agonist administration in MLNR transgenic mice.

Academic Significance and Societal Importance of the Research Achievements

モチリン受容体アゴニストが，種々の疾患や薬物による消化管運動機能障害を改善することから，現在モチリン受容体アゴニストとして臨床使用が可能なエリスロマイシン治療の有用性が確立された。またモチリン受容体TGマウスは，消化管運動機能改善物質のスクリーニングに有用なシステムであることが明らかとなった。

Research Products

• [Int'l Joint Research] Mayo Clinic Arizona(米国)
• [Int'l Joint Research] Mayo Clinic Arizona(米国)
• [Journal Article] Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice (2019)
  • Author(s): Kato S, Takahashi A, Shindo M, Yoshida A, Kawamura T, Matsumoto K, Matsuura B
  • Journal Title: ProS One Volume: 14 Issue: 2 Pages: e0205939-e0205939
  • DOI: 10.1371/journal.pone.0205939
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Motilin Receptor Agonists and Ghrelin in Human motilin receptor Transgenic Mice (2019)
  • Author(s): Kawamura T, Matsuura B, Miyake T, Abe M, Ikeda Y, Hiasa Y
  • Journal Title: Int J Mol Sci Volume: 20 Issue: 7 Pages: 1521-1521
  • DOI: 10.3390/ijms20071521
  • Peer Reviewed / Open Access
• [Journal Article] Depletion of B cell-activating factor attenuates hepatic fat accumulation in a murine model of nonalcoholic fatty liver disease (2019)
  • Author(s): Nakamura Y, Abe M, Kawasaki K, Miyake T, Watanabe T, Yoshida O, Hirooka M, Matsuura B, Hiasa Y
  • Journal Title: Sci Rep Volume: 9 Issue: 1 Pages: 977-977
  • DOI: 10.1038/s41598-018-37403-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Free testosterone concentration is inversely associated with markers of liver fibrosis in men with type 2 diabetes mellitus (2017)
  • Author(s): Miyauchi S, Miyake T, Miyazaki M, Eguchi T, Niiya T, Yamamoto S, Senba H, Furukawa S, Matsuura B, Hiasa Y
  • Journal Title: Endocrine Journal Volume: 64 Issue: 12 Pages: 1137-1142
  • DOI: 10.1507/endocrj.EJ17-0225
  • NAID: 130006287808
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Upregulated absorption of dietary palmitic acids with changes in intestinal transporters in non-alcoholic steatohepatitis (NASH) (2017)
  • Author(s): Utsunomiya H, Yamamoto Y, Takeshita E, Tokumoto Y, Tada F, Miyake T, Hirooka M, Abe M, Kumagi T, Matsuura B, Ikeda Y, Hiasa Y
  • Journal Title: J Gastroenterol Volume: 印刷中 Issue: 8 Pages: 940-954
  • DOI: 10.1007/s00535-016-1298-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Metabolic surgery後の肝脂肪量の変化についての検討 (2019)
  • Author(s): 仙波英徳，山本晋，松浦文三
  • Organizer: 第105回日本消化器病学会総会
• [Presentation] 糖尿病診療における最近の話題 (2019)
  • Author(s): 松浦文三
  • Organizer: 第60回日本内科学会四国支部生涯教育講演会
  • Invited
• [Presentation] 肥満症の食事療法 (2019)
  • Author(s): 松浦文三
  • Organizer: 日本肥満学会 肥満症サマーセミナー
  • Invited
• [Presentation] ヒトモチリン受容体トランスジェニックマウスにおける発現局在および胃運動性の解析 (2018)
  • Author(s): 加藤伸一，高橋葵，吉田彩乃，松本健次郎，天ケ瀬紀久子，松浦文三
  • Organizer: 日本薬学会第138年会
• [Presentation] Desensitization of the human motilin receptor by motilin and motilides (2018)
  • Author(s): Matsuura B, Takano A, Kawamura T, Yamamoto S, Senba H, Miyake T, Furukawa S, Abe M, Hiasa Y
  • Organizer: 20th European Congress of Endocrinology
  • Int'l Joint Research
• [Presentation] Human motilin receptor transgenic mice are useful for evaluation of motilin receptor agonists as gastric prokinetic drugs (2018)
  • Author(s): Kato S, Takahashi A, Shindo M, Matsumoto K, Amagase K, Matsuura B
  • Organizer: 18th World Congress of Basic and Clinical Pharmacology
  • Int'l Joint Research
• [Presentation] 食事中脂肪酸分画の違いが肝癌発症に及ぼす影響の検討 (2018)
  • Author(s): 三宅映己，吉田理，廣岡昌史，竹下英治，熊木天児，阿部雅則，松浦文三，日浅陽一
  • Organizer: JDDW 2018
• [Presentation] Intensive treatment for obesity at our hospital (2018)
  • Author(s): Matsuura B, Senba H, Yamamoto S, Miyake T, Hiasa Y, Koga S, Yoshida M, Watanabe Y
  • Organizer: Asia Pacific Metabolic and Bariatric Surgery Society Congress 2018
  • Int'l Joint Research
• [Presentation] Increase of serum chylomicron triglyceride concentration associated with intestinal overproduction of chylomicron triglyceride in nonobese, nondiabetic and normolipidemic NASH patients. (2017)
  • Author(s): Utsunomiya N, Hanayama M, Yamamoto Y, Takeshita E, Tokumoto Y, Miyake T, Hirooka M, Kumagi T, Matsuura B, Abe M, Ikeda Y, Hiasa Y
  • Organizer: AASLD meeting 2017
  • Int'l Joint Research
• [Book] 日本病態栄養学会編：がん栄養療法ガイドブック2019 改訂第2版 (2019)
  • Author(s): 松浦文三，利光久美子
  • Publisher: 南江堂
  • ISBN: 9784524246281
• [Book] 矢崎義雄編：内科学第11版 (2017)
  • Author(s): 松浦文三
  • Publisher: 朝倉書店
• [Remarks] 愛媛大学 大学院医学系研究科 医学専攻 地域生活習慣病・内分泌学
  • URL: https://www.m.ehime-u.ac.jp/course/
• [Remarks] 愛媛大学大学院医学系研究科 消化器・内分泌・代謝内科学
  • URL: https://www.m.ehime-u.ac.jp/school/int.med3/
• [Remarks] https://www.m.ehime-u.ac.jp/school/int.med3/