Pathophysiological role of uridine adenosine tetraphosphate in diabetic vasculopathy

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790265
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Hoshi University
• Principal Investigator: MATSUMOTO Takayuki 星薬科大学, 薬学部, 講師 (30366835)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 糖尿病 / 血管機能障害 / 血管平滑筋細胞 / 血管内皮細胞

Research Abstract

We have assessed responses to Up4A, a novel endothelium-derived contracting factor, shown by renal arteries (RAs) from type 2 diabetic Goto-Kakizaki (GK) rats. Up4A-induced contraction was greater in RA from the GK (vs. age-matched Wistar control). Inhibition of nitric oxide synthase increased the response to Up4A, whereas cyclooxygenase (COX) inhibition, antagonism of thromboxane (TX) receptor (TP) and P2 receptor decreased the response. In GK RA (vs. Wistar) ,COXs expression and TP agonist-induced contraction were greater, whereas the production of TXA2 by Up4A did not differ between groups.
Our data indicate that the Up4A-induced contraction is closely associated with activation of COX/TP receptor axis. Clarifying the signal transduction and control of vascular tone by Up4A may be of significance to understanding the patho- physiology and advancing treatment of diabetes-associated vascular complications.

Research Products

• [Journal Article] Enhanced uridine adenosine tetraphosphate-induced contraction in renal artery from type 2 diabetic Goto-Kakizaki rats due to activated cyclooxygenase/thromboxane receptor axis (2014)
  • Author(s): Matsumoto T, Watanabe S, Kawamura R, Taguchi K, Kobayashi T
  • Journal Title: Pflugers Arch Volume: 466 Pages: 331-42
  • DOI: 10.1007/s00424-013-1330-0
  • Peer Reviewed
• [Journal Article] Relationships among protein tyrosine phosphatase 1B, angiotensin II, and insulin-mediated aortic responses in type 2 diabetic Goto-Kakizaki rats (2014)
  • Author(s): Nemoto S, Matsumoto T, Taguchi K, Kobayashi T
  • Journal Title: Atherosclerosis Volume: 233 Pages: 64-71
  • DOI: 10.1016/j.atherosclerosis.2013.12.032
  • Peer Reviewed
• [Journal Article] Epigallocatechin gallate attenuates ET-1-induced contraction in carotid artery from type 2 diabetic OLETF rat at chronic stage of diabetes (2014)
  • Author(s): Matsumoto T, Watanabe S, Kawamura R, Taguchi K, Kobayashi T
  • Journal Title: Life Sci Volume: (in press)
  • DOI: 10.1016/j.lfs.2013.11.016
  • Peer Reviewed
• [Presentation] 2型糖尿病ラット摘出頸動脈におけるエンドセリン-1収縮に対するエピガロカテキンガレート慢性投与の影響 (2014)
  • Author(s): 松本貴之, 渡邊駿, 川村隆輔, 金津智絵, 鳥羽美貴子, 新井隆三, 上原千晶, 佐川なつ実, 山田浩介, 田口久美子, 小林恒雄
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本大学
  • Year and Date: 20140327-30
• [Presentation] Increased Up4A-induced contraction in type 2 diabetic renal artery due to activated COX/thromboxane receptor axis (2014)
  • Author(s): 松本貴之, 渡邊駿, 田口久美子, 小林恒雄
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 東北大学、仙台国際センター
  • Year and Date: 20140319-21
• [Presentation] Epigallocatechin gallate attenuates ET-1-induced contraction in carotid and thoracic aorta from type 2 diabetic OLETF rat (2013)
  • Author(s): Matsumoto T, Watanabe S, Kawamura R, Kobayashi T
  • Organizer: Thirteenth International Conference on Endothelin
  • Place of Presentation: University of Tsukuba, Tokyo Campus
  • Year and Date: 20130908-11
• [Presentation] 新規内皮由来収縮因子ウリジンアデノシンテトラフォスフェートの2型糖尿病ラット腎動脈における収縮反応性の変化 (2013)
  • Author(s): 松本貴之, 渡邊駿, 川村隆輔, 名取世津子, 森真里英, 藤井真理子, 松葉優矢, 小林恒雄
  • Organizer: 第55回日本平滑筋学会総会
  • Place of Presentation: 旭川市大雪クリスタルホール
  • Year and Date: 20130806-08
• [Presentation] 2型糖尿病ラット摘出腎動脈におけるuridine adenosine tetraphosphateによる収縮反応の検討 (2013)
  • Author(s): 松葉優矢, 松本貴之, 渡邊駿, 森真里英, 名取世津子, 川村隆輔, 藤井真理子, 小林恒雄
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20130327-30
• [Presentation] 2型糖尿病ラット摘出頸動脈におけるセロトニンによる収縮反応性の検討 (2013)
  • Author(s): 渡邊駿, 松本貴之, 松葉優矢, 名取世津子, 森真里英, 藤井真理子, 川村隆輔, 小林恒雄
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20130327-30
• [Presentation] 2型糖尿病ラット(GKラット)腎動脈における新規内皮由来収縮因子Up4Aの収縮反応とthromboxane A2シグナルの関連 (2013)
  • Author(s): 渡邊駿, 松本貴之, 田口久美子, 小林恒雄
  • Organizer: 第57回日本薬学会関東支部大会
  • Place of Presentation: 帝京大学
  • Year and Date: 2013-10-26