The mechanism of novel LPA3-mediated activation of vagal afferent nerve

• Project/Area Number: 16K18870
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Tohoku University
• Principal Investigator: Kano Kuniyuki 東北大学, 薬学研究科, 助教 (50636404)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: リゾホスファチジン酸 / 迷走神経 / 心筋梗塞 / ドコサヘキサエン酸 / リゾリン脂質

Outline of Final Research Achievements

Imaging MS and LC-MS/MS analysis revealed that lysophosphatidic acid (LPA) containing docosahexaenoic acid (DHA (22:6)) was selectively elevated in the ischemic heart. Administration of autotaxin (ATX) inhibitor did not affect the increase of DHA-LPA, suggesting that DHA-LPA was produced in ATX-independent manner.
LPA3 agonist induced a transient apnea and a prolonged hypopnea, which is resulted from activation of vagus nerve. We also found novel pharmacological action of LPA3 agonist independent on vagus nerve.

Research Products

• [Journal Article] Different Origins of Lysophospholipid Mediators between Coronary and Peripheral Arteries in Acute Coronary Syndrome. (2017)
  • Author(s): Kurano, M., Kano, K., Dohi, T., Matsumoto, H., Igarashi, K., Nishikawa, M., Ohkawa, R., Ikeda, H., Miyauchi, K., Daida, H., Aoki, J., and Yatomi, Y.
  • Journal Title: J. Lipid Res. Volume: 58 Issue: 2 Pages: 433-442
  • DOI: 10.1194/jlr.p071803
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Imaging MS analysis of lysophospholipids using AP-MALDI-MS (2017)
  • Author(s): Kuniyuki Kano, Daisuke Saigusa and Junken Aoki
  • Organizer: Keystone symposia
  • Place of Presentation: California (USA)
  • Year and Date: 2017-02-26
  • Int'l Joint Research
• [Presentation] Imaging MS analysis of lysophospholipids using AP-MALDI-MS (2017)
  • Author(s): Kuniyuki Kano, Daisuke Saigusa and Junken Aoki
  • Organizer: FASEB Science Research Conference
  • Int'l Joint Research
• [Presentation] Imaging MS analysis of lysophospholipids using AP-MALDI-MS (2017)
  • Author(s): Kuniyuki Kano, Daisuke Saigusa and Junken Aoki
  • Organizer: Bioactive lipids conference
  • Int'l Joint Research
• [Presentation] An emerging role of DHA-containing LPA in myocardial infarction (2017)
  • Author(s): Kuniyuki Kano, Junken Aoki
  • Organizer: International Conference on Lipoquality
  • Int'l Joint Research / Invited
• [Presentation] Preventive and alleviative effects of LPA3 signaling in a novel mouse model of acute exacerbation of idiopathic pulmonary fibrosis (2017)
  • Author(s): Naoki Omae, Kuniyuki Kano, Junken Aoki
  • Organizer: FASEB Science Research Conference
  • Int'l Joint Research
• [Presentation] Lysophosphatidic acid enhances IL-10 production in a mouse LPS model (2017)
  • Author(s): Jiao Wang, Kuniyuki Kano, Kyoko Satake, Junken Aoki
  • Organizer: Keystone Symposia on Lipidomics and Bioactive Lipids in Metabolism and Disease
  • Int'l Joint Research
• [Presentation] Lysophosphatidic acid stimulates IL-10 production from murine peritoneal macrophage (2017)
  • Author(s): Jiao Wang, Kuniyuki Kano, Junken Aoki
  • Organizer: BMB2017
• [Presentation] リゾリン脂質メディエーターリゾホスファチジン酸の新規迷走神経刺激因子としての機能 (2016)
  • Author(s): 可野邦行
  • Organizer: 日本薬学会東北支部若手研究者セミナー
  • Place of Presentation: 仙台
  • Invited