Modulation of swallowing reflex by an endocannabinoid-degrading enzyme inhibitor (JZL184).

• Project/Area Number: 26462808
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Matsumoto Dental University (2015-2016); Niigata University (2014)
• Principal Investigator: Kitagawa Junichi 松本歯科大学, 歯学部, 教授 (50373006)
• Co-Investigator(Kenkyū-buntansha): 篠田 雅路 日本大学, 歯学部, 准教授 (20362238)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 嚥下 / 嚥下障害 / 内因性カンナビノイド / 2-AG / 内因性カンナビノイド分解酵素阻害剤 / JZL184 / 上喉頭神経 / 嚥下中枢

Outline of Final Research Achievements

The present study was designed to investigate whether swallowing reflex in rat is modulated by JZL184, an inhibitor of the main degradation enzyme of a major endocannabinoid named 2-arachydonoylglycerol (2-AG). Intrathecal (IT) application of JZL184 reduced the latency of onset of swallowing reflex evoked by electrical stimulation of the superior laryngeal nerve (SLN). Findings of immunohistochemical study indicated that JZL184 application (IT) reduced production of the degradation enzyme monoacylglycerol lipase (MAGL), thereby increased the accumulation of 2-AG in the swallowing center of the nucleus tractus solitaries. These findings suggest that increase accumulation of endocannabinoid by preventing its degradation in the swallowing center can facilitate the triggering of swallowing reflex.

Research Products

• [Journal Article] Inhibition of the degradation of 2-arachydonoylglycerol (2-AG) attenuated orofacial neuropathic pain following an injury to the trigeminal nerve in mice. (2017)
  • Author(s): Kamimura R, Hossain MZ, Unno S, Ando H, Masuda Y, Takahashi K, Otake M, Saito I, Kitagawa J
  • Journal Title: J Oral Sci. Volume: 印刷中 Issue: 2 Pages: 4-4
  • DOI: 10.1111/adj.12484
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Involvement of microglia and astroglia in modulation of the orofacial motor functions in neuropathic-pain rats. (2016)
  • Author(s): Zakir HM, Shinoda M, Unno S, Ando H, Masuda Y, Iwata K, Kitagawa J
  • Journal Title: JOB. Volume: 59 Pages: 7-12
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Distribution and origin of VIP-, SP-, and phospholipase Cβ2 - immunoreactive nerves in the tongue of the bullfrog, Rana catesbeiana. (2016)
  • Author(s): Tadokoro O, Ando H, Kawahara I, Asanuma N, Okumura M, Kitagawa J, Kondo E, Yagasaki H
  • Journal Title: Anat Rec (Hoboken). Volume: 299 Issue: 7 Pages: 929-942
  • DOI: 10.1002/ar.23334
  • Peer Reviewed
• [Journal Article] Muscle Spindles Provide Servo-assistance to Jaw-closing Muscles for Chewing Hard Foods. (2015)
  • Author(s): Zakir HM, Kitagawa J, Fathilah AR, Bakri MM
  • Journal Title: Sains Malaysiana Volume: 44 Pages: 593-597
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Physiological and pharmacological actions involved in the pharyngeal and laryngeal sensation (2015)
  • Author(s): Takatsuji H, Takahashi K, Kitagawa J
  • Journal Title: Folia Pharmacologica Japonica Volume: 145 Issue: 6 Pages: 278-282
  • DOI: 10.1254/fpj.145.278
  • NAID: 130005075724
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 咽頭・喉頭感覚が関与する生理・薬理作用 (2015)
  • Author(s): 高辻華子，高橋功次朗，北川純一
  • Journal Title: 日本薬理学雑誌 Volume: 145
  • NAID: 130005075724
  • Peer Reviewed
• [Presentation] Immunohistochemical and electrophysiological evidence of activity of TRPV1 and TRPM8 in the superior laryngeal nerve innervating the laryngopharynx and associated laryngeal regions. (2016)
  • Author(s): Hossain MZ, Ando H, Unno S, Kondo E, Masuda Y, Kitagawa J
  • Organizer: 第10回三叉神経研究会
  • Place of Presentation: 佐久平プラザ21（長野県佐久市）
  • Year and Date: 2016-11-26
• [Presentation] TRPV1 and TRPM8 channels expression and activity in the superior laryngeal nerve innervating the laryngopharynx and associated laryngeal regions: an immunohistochemical and electrophysiological study. (2016)
  • Author(s): Hossain MZ, Ando H, Unno S, Masuda Y, Kitagawa J
  • Organizer: Oral Neuroscience 2016
  • Place of Presentation: 大阪大学歯学部（大阪府吹田市）
  • Year and Date: 2016-10-01
• [Presentation] Integration of sensory and motor function in the orofacial region. (2016)
  • Author(s): Kitagawa J
  • Organizer: Oral Neuroscience 2016
  • Place of Presentation: 大阪大学歯学部（大阪府吹田市）
  • Year and Date: 2016-10-01
  • Invited
• [Presentation] 喉頭領域を支配する上喉頭神経におけるTRPV1 およびTRPM8 チャネルの発現. (2016)
  • Author(s): 安藤宏，増田裕次，北川純一
  • Organizer: 第58回歯科基礎医学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-08-24
• [Presentation] 三叉神経運動核アストログリアは眼窩下神経損傷による開口反射の変調に関与する. (2015)
  • Author(s): 北川純一
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟市）
  • Year and Date: 2015-09-11
  • Invited
• [Presentation] 咽頭・喉頭領域の感覚受容と 「こく」 (2014)
  • Author(s): 北川純一
  • Organizer: 日本食品科学工学会第61回大会
  • Place of Presentation: 中村学園大学（福岡市）
  • Year and Date: 2014-08-29
  • Invited