1998 Fiscal Year Annual Research Report

血管内皮細胞におけるATP遊離機構とCa^<2+>動員機構の局在性に関する研究

Research Project

Project/Area Number	09670112
Research Institution	Mukogawa Women's University
Principal Investigator	篠塚和正武庫川女子大学, 薬学部, 助教授 (50117777)
Keywords	ATP / ラット尾動脈 / α_1アドレナリン受容体 / カルシウムイオン / ギャップジャンクション / 一酸化窒素 / 培養内皮細胞
Research Abstract	ラット尾動脈内皮細胞におけるATP遊離機構とCa^<2+>動員機構の関連性について,画像解析装置および,ATP可視化技術を用いて,以下の3点について検討した。【1】 ATP遊離機構とCa^<2+>動員機構の機能的接点:血管組織標本において、ノルアドレナリン(NA)のα_1受容体刺激により遊離されるATPは内皮に由来するとともに,外液Ca^<2+>依存性であり電位依存性でもあった。さらにこのATP遊離はGap Junctionの機能を低下させると考えられている高浸透圧条件下及びGap Junction阻害薬(1-heptanol)の存在下で消失した。【2】 ATP遊離機構とCa^<2+>動員機構の空間的接点:血管組織標本において、NAは内皮及び平滑筋の細胞内Ca^<2+>レベル([Ca^<2+>]i)を共に著明に上昇させたが、培養内皮細胞においては、NAによる[Ca^<2+>]i上昇は観察されず,ATP遊離も極めて微量であった。【3】 ATP遊離機構とNO産生放出機構との機能的空間的接点:血管組織標本において内皮依存性弛緩反応(L-NAME感受性)を惹起するブラジキニン(BK)は内皮の[Ca^<2+>]iを著明に上昇させたが、ATPの遊離を全く惹起しなかった。また,培養内皮細胞においても,同様に[Ca^<2+>]iを上昇させたが、ATPの遊離は惹起しなかった。以上の結果より、α_1受容体に連関したATP遊離機構には,内皮細胞のCa^<2+>動員機構に加え平滑筋細胞のCa^<2+>動員機構も関与していること、さらに両細胞間のGap Junctionが重要な役割を果たしているのではないかという新しい可能性が示唆された。従ってATP遊離機構とNOの遊離機構に連関する細胞内のCa^<2+>動員機構の違いは、Gap Junctionの関与の有無による可能性が推察され、この点は内皮と平滑筋細胞の相互作用を解明する上でも今後検討すべき重要な課題であると思われる。

Research Products
(13 results)

All Other

All Publications (13 results)

[Publications] Shinozuka K.et al.: "Effects of TRH and its analogue,NS-3,on blood pressure,heart rate,and serum catecholamine levels in rats." General Pharmacology. 28(2). 209-214 (1997)
[Publications] Hashimoto M.et al.: "Source of ATP,ADP,AMP and adenosine released from isolated rat caudal artery exposed to noradrenaline" Journal of Smooth Muscle Research. 33(3). 127-133 (1997)
[Publications] Shinozuka K.et al.: "Regional differences in noradrenaline-induced release of ATP from isolated vascular endothelium" Journal of Smooth Muscle Research. 33(4). 135-143 (1997)
[Publications] Tong,Y.C.et al.: "Evidence of ATP release from nerve and P2x-purinoceptor mediated contraction druing electrical stimulation of rat urinary bladder smooth muscle" Journal of Urology. 158. 1973-1977 (1997)
[Publications] Hashimoto M.et al.: "Antihypertensive effect of EPA of aged rats is associated with an increase in the release of ATP from the caudal artery" Journal of Vascular Research. 35. 55-62 (1998)
[Publications] Kagota S.et al.: "Mechanisms of impairment of endothelium-dependent relaxation to ACh in WHHL rabbit aortas" Clinical and Experimental Pharmacology and Physiology. 25. 104-109 (1998)
[Publications] 佐々木哲也他: "ATP感受性K+チャネル開口薬は冠動脈内皮細胞からのプリン誘導体の遊離を促進する" Therapeutic Research. 19(4). 23-28 (1998)
[Publications] Shinozuka K.et al.: "Possible participation of ATP in changes of the blood pressure of SHR and old rats" Japanese Heart Journal. 39(4). 535-537 (1998)
[Publications] Kowamoto Y.et al.: "Determination of ATP and its metabolites released from rat caudal artery by isocratic ion-pair reverse -phase HPLC" Analytical Biochemistry. 262(1). 33-38 (1998)
[Publications] Hashimoto M.et al.: "Long-term supplementation of high cholesterol diet to aged rats decreases the release of ATP from the caudal artery" Life Science. 63(21). 1879-1885 (1998)
[Publications] Hashimoto M.et al.: "Association of hypotensive effect of DHA with enhanced release of ATP from caudal artery of aged rat" The Journal of Nutrition. 129. 70-76 (1998)
[Publications] Hashimoto M.et al.: "Antihypertensive effect of exercise on aged rats associated with enhanced ATP release from the caudal artery" American Journal of Physiology. (in press).
[Publications] Kwon Y.M.et al.: "Both of the extracellular ATP and shear stress regulate the release of NO in rat caudal artery" Clinical and Experimental Pharmacology and Physiology. (in press).

1998 Fiscal Year Annual Research Report

血管内皮細胞におけるATP遊離機構とCa^<2+>動員機構の局在性に関する研究

Principal Investigator

篠塚 和正 武庫川女子大学, 薬学部, 助教授 (50117777)

Research Products

[Publications] Shinozuka K.et al.: "Effects of TRH and its analogue,NS-3,on blood pressure,heart rate,and serum catecholamine levels in rats." General Pharmacology. 28(2). 209-214 (1997)

[Publications] Hashimoto M.et al.: "Source of ATP,ADP,AMP and adenosine released from isolated rat caudal artery exposed to noradrenaline" Journal of Smooth Muscle Research. 33(3). 127-133 (1997)

[Publications] Shinozuka K.et al.: "Regional differences in noradrenaline-induced release of ATP from isolated vascular endothelium" Journal of Smooth Muscle Research. 33(4). 135-143 (1997)

[Publications] Tong,Y.C.et al.: "Evidence of ATP release from nerve and P2x-purinoceptor mediated contraction druing electrical stimulation of rat urinary bladder smooth muscle" Journal of Urology. 158. 1973-1977 (1997)

[Publications] Hashimoto M.et al.: "Antihypertensive effect of EPA of aged rats is associated with an increase in the release of ATP from the caudal artery" Journal of Vascular Research. 35. 55-62 (1998)

[Publications] Kagota S.et al.: "Mechanisms of impairment of endothelium-dependent relaxation to ACh in WHHL rabbit aortas" Clinical and Experimental Pharmacology and Physiology. 25. 104-109 (1998)

[Publications] 佐々木哲也他: "ATP感受性K+チャネル開口薬は冠動脈内皮細胞からのプリン誘導体の遊離を促進する" Therapeutic Research. 19(4). 23-28 (1998)

[Publications] Shinozuka K.et al.: "Possible participation of ATP in changes of the blood pressure of SHR and old rats" Japanese Heart Journal. 39(4). 535-537 (1998)

[Publications] Kowamoto Y.et al.: "Determination of ATP and its metabolites released from rat caudal artery by isocratic ion-pair reverse -phase HPLC" Analytical Biochemistry. 262(1). 33-38 (1998)

[Publications] Hashimoto M.et al.: "Long-term supplementation of high cholesterol diet to aged rats decreases the release of ATP from the caudal artery" Life Science. 63(21). 1879-1885 (1998)

[Publications] Hashimoto M.et al.: "Association of hypotensive effect of DHA with enhanced release of ATP from caudal artery of aged rat" The Journal of Nutrition. 129. 70-76 (1998)

[Publications] Hashimoto M.et al.: "Antihypertensive effect of exercise on aged rats associated with enhanced ATP release from the caudal artery" American Journal of Physiology. (in press).

[Publications] Kwon Y.M.et al.: "Both of the extracellular ATP and shear stress regulate the release of NO in rat caudal artery" Clinical and Experimental Pharmacology and Physiology. (in press).

篠塚和正武庫川女子大学, 薬学部, 助教授 (50117777)