1998 Fiscal Year Annual Research Report

血管の細胞シグナル伝達網制御を多項目連続測定可能な光学システムの開発

Research Project

Project/Area Number	10557072
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	Kyushu University
Principal Investigator	金出英夫九州大学, 医学部, 教授 (80038851)
Co-Investigator(Kenkyū-buntansha)	平野勝也九州大学, 医学部, 講師 (80291516) 西村淳二九州大学, 医学部, 助教授 (90237727)
Keywords	細胞シグナル伝達 / 血管内皮細胞 / 血管平滑筋細胞 / fura-2 / タプシガルギン / 容量依存性性カルシウム流入 / 血管緊張調節
Research Abstract	本研究の目的は、血管の細胞(内皮細胞、平滑筋細胞)シグナル伝達網([Ca]i、c-AMP、c-GMP、[Na]i、pH)やエネルギー代謝(NADH)変化と、種々の血管機能(NO産生・緊張・増殖等)を、可能なかぎり同時連続観察できる光学システムを開発することにある。このシステムを用いて、血管の緊張や増殖制御機序とその異常を解明し、さらには血管作動薬の作用機序を明かにしたい。本年度は以下の成果を得た。(1)シリーズ「METHODS IN MOLECULAR BIOLOGY」の1分冊「Calcium Signaling Protocols」の1章「Measurement of [Ca_<2+>]i in smooth muscle strips using front-surface fluorimetry」として我々の[Ca]i測定法が広く紹介された(THE HUMANA PRESS INC.,N.J.,U.S.A.,1999,1刊行)。(2)腎動脈において、1μMフェニレフリンによる持続収縮中に1μMタプシガルギンを投与すると、内皮細胞の容量性Ca流入を伴って、3相性の内皮依存性血管緊張反応が引き起こされた。すなわち、平滑筋の[Ca]i低下を伴った初期の一過性弛緩、[Ca]i上昇を伴った一過性収縮、[Ca]i変化を伴わない持続的弛緩が認められた。L-NAMEの前処置によって、初期一過性弛緩相は部分的に、持続的弛緩相は完全に抑制された。TXA_2/PGH_2受容体遮断薬(ONO-3708)およびインドメタシンの前処置によって一過性収縮相は抑制された。インドメタシンとL-NAMEで前処置した血管標本でも、フェニレフリンで前収縮させる場合には、タプシガルギンは初期の一過性弛緩を引き起こすが、118mM K脱分極刺激で前収縮させる場合には、タプシガルギンによるこの弛緩は消失した。この結果、タプシガルギンが引き起こす豚腎動脈の内皮依存性血管反応においては、一過性収縮には主としてTXA_2が、初期の弛緩にはEDHFとNOが、持続的弛緩にはNOが関与することが明らかとなった。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Zhou YB: "Expression and function of α_1-adrenoceptor subtypes in the porcine renal artery." Eur J Pharmacol. 341. 95-103 (1998)
[Publications] Ahmed A: "Differential effects of Ca^<2+> channel blockers on Ca^<2+> transients and cell cycle progression in vascular smooth muscle cells." Eur J Pharmacol. 344. 323-331 (1998)
[Publications] Seguchi H: "Expression of β3-adrenoceptors in rat detrusor smooth muscle." J Urology. 159. 2197-2201 (1998)
[Publications] Mizuno O: "Mechanism of endothelium-dependent relaxation induced by thrombin in the pig coronary artery." Eur J Pharmacol. 351. 67-77 (1998)
[Publications] Niiro N: "Mechanisms and mode of action for galanin-induced contraction in the rat myometrium." Br J Pharmacol. 124. 1623-1632 (1998)
[Publications] Kawasaki J: "Mechanisms of vasorelaxation induced by troglitazone, a novel anti-diabetics, in the porcine coronary aretery." Circulation. 98. 2446-2452 (1998)
[Publications] Hirano M: "Expression, subcellular localization and cloning of the 130kDa regulatory subunit of myosin phosphatase in porcine aorlic endothelial cells." Biochem Biophys Res Commun. 254. 490-496 (1999)
[Publications] Yasutsune T: "Vasorelaxation and inhibition of the voltage-operated Ca^<2+> channels by FK506 in porcine coronary artery." Br J Pharmacol. in press.
[Publications] Zhou YB: "The exogenously added small subunit of smooth muscle myosin phosphatase increases the Ca^<2+> sensitivity of the contractile apparatus in the permeabilized porcine renal artery." Biochem Biophys Res Commun. in press.
[Publications] Zhou YB: "NH_2-terminal fragments of 130 kDa subunit of myosin phosphatase increases Ca^<2+> sensitivity of the porcine renal artery." J Physiol. in press.
[Publications] Kanaide H: "Methods in Molecular Biology, Vol.114: Calcium Signaling Protocols, Edited by :DG Lambert" Humana Press Inc., Totowa, NJ, 269-277 (1999)

1998 Fiscal Year Annual Research Report

血管の細胞シグナル伝達網制御を多項目連続測定可能な光学システムの開発

Principal Investigator

金出 英夫 九州大学, 医学部, 教授 (80038851)

Research Products

[Publications] Zhou YB: "Expression and function of α_1-adrenoceptor subtypes in the porcine renal artery." Eur J Pharmacol. 341. 95-103 (1998)

[Publications] Ahmed A: "Differential effects of Ca^<2+> channel blockers on Ca^<2+> transients and cell cycle progression in vascular smooth muscle cells." Eur J Pharmacol. 344. 323-331 (1998)

[Publications] Seguchi H: "Expression of β3-adrenoceptors in rat detrusor smooth muscle." J Urology. 159. 2197-2201 (1998)

[Publications] Mizuno O: "Mechanism of endothelium-dependent relaxation induced by thrombin in the pig coronary artery." Eur J Pharmacol. 351. 67-77 (1998)

[Publications] Niiro N: "Mechanisms and mode of action for galanin-induced contraction in the rat myometrium." Br J Pharmacol. 124. 1623-1632 (1998)

[Publications] Kawasaki J: "Mechanisms of vasorelaxation induced by troglitazone, a novel anti-diabetics, in the porcine coronary aretery." Circulation. 98. 2446-2452 (1998)

[Publications] Hirano M: "Expression, subcellular localization and cloning of the 130kDa regulatory subunit of myosin phosphatase in porcine aorlic endothelial cells." Biochem Biophys Res Commun. 254. 490-496 (1999)

[Publications] Yasutsune T: "Vasorelaxation and inhibition of the voltage-operated Ca^<2+> channels by FK506 in porcine coronary artery." Br J Pharmacol. in press.

[Publications] Zhou YB: "The exogenously added small subunit of smooth muscle myosin phosphatase increases the Ca^<2+> sensitivity of the contractile apparatus in the permeabilized porcine renal artery." Biochem Biophys Res Commun. in press.

[Publications] Zhou YB: "NH_2-terminal fragments of 130 kDa subunit of myosin phosphatase increases Ca^<2+> sensitivity of the porcine renal artery." J Physiol. in press.

[Publications] Kanaide H: "Methods in Molecular Biology, Vol.114: Calcium Signaling Protocols, Edited by :DG Lambert" Humana Press Inc., Totowa, NJ, 269-277 (1999)

金出英夫九州大学, 医学部, 教授 (80038851)