Study of ATP-sensitive potassium channel in constriction of ductus arteriosus

• Project/Area Number: 26461648
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Ishii Tetsuko 東京女子医科大学, 医学部, 講師 (00360157)
• Co-Investigator(Kenkyū-buntansha): 羽山 恵美子 東京女子医科大学, 医学部, 非常勤講師 (00349698) ; 中西 敏雄 東京女子医科大学, 医学部, 特任教授 (90120013)
• Co-Investigator(Renkei-kenkyūsha): MOMMA Kazuo 東京女子医科大学, 医学部・循環器小児科, 名誉教授 (80075233)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 動脈管 / KATP channel / ATP感受性Kチャネル / SUR2 / KATPチャネル

Outline of Final Research Achievements

ATP-sensitive potassium channels expressed in vascular smooth muscle cells are mainly composed of Kir6.1 and SUR2 subunits. Expression of Kir6.1 and SUR2 transcripts in ductus arteriosus (DA), main pulmonary artery (PA), and descending aorta (dAo) in rat immature and mature fetuses, and newborns were determined using real-time PCR. Both Kir6.1 and SUR2 transcripts are expressed in the DA higher than PA and dAo in the fetuses and newborns. Unidentified SUR2 transcript variants are expressed in the immature fetal DA, specifically.
Glibenclamide, an inhibitor of ATP-sensitive potassium channel, directly injected intraperitoneally to fetus rats, constricted DA in near-term and preterm. Effect of glibenclamide in the DA was dose-dependently. With clinical dose (1mg/kg), DA diameter was 70%, and with 100mg/kg, DA closed completely. Glibenclamide closes neonatal DA dose-dependently in hypoxia but not following prenatal chronic exposure to indomethacin.

Research Products

• [Journal Article] 動脈管薬の実験40年 (2016)
  • Author(s): 門間和夫
  • Journal Title: 日本小児循環器学会雑誌 Volume: 32 Pages: 261-269
  • NAID: 130005256742
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Glibenclomid closes neonatal ductus arteriosus in rats. (2014)
  • Author(s): Momma K, Toyoshima K, Hayama E, Nakanishi T
  • Organizer: Fifth European Academy of Pediatrics
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-10-17 – 2014-10-21
• [Presentation] インドメタシン母体投与による未熟児PDAラットモデルにおけるスルホニル尿素薬の動脈管収縮促進作用 (2014)
  • Author(s): 豊島勝昭,門間和夫, 門間美佳,石井徹子,中西敏雄
  • Organizer: 第8回新生児内分泌研究会
  • Place of Presentation: 京都リサーチパークサイエンスホール
  • Year and Date: 2014-09-13
• [Presentation] 動脈管の研究40年 (2014)
  • Author(s): 門間和夫
  • Organizer: 第50回日本小児循環器学会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2014-07-04
  • Invited
• [Book] Etiology and Morphogenesis of Congenital Heart Disease. (2016)
  • Author(s): Momma K, Monma M, Toyoshima K, Hayama E, Nakanishi T.
  • Publisher: Springer, Japan.