Cellular Pharmacology of Hyperpolarization-Relaxation Coupling

超极化弛豫耦合的细胞药理学

• 批准号: 07457020
• 负责人: YANAGISAWA Teruyuki
• 金额: $ 4.74万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457020/
• 关键词: K^+ channels; Hyperpolarization; Relaxation; K^+ channel openers; K^+ channel blockers; intracellular CaX^<2+> concentration; Coronary artery; Cerbral artery; レボクロマカリム; ベラパミル; カリウムチャネル開口薬(オープナ-)

The involvement of large conductance Ca^<2+>-activated K^+ channels (BK) and ATP-sensitive K^+ (K_<ATP>) channels in regulation of arterial tone was examined by measuring the change in intracellular Ca^<2+> concentration ([Ca^<2+>]_i) simultaneously with force of contraction in the canine or porcine coronary or basilar arterial smooth muscles. At resting condition, levcromakalim reduced [Ca^<2+>]_i and tone. Levcromakalim suppressed the serotonin-induced increases in [Ca^<2+>]_i and contraction, the maximum effects of which were much greater than those of nicardipine. The inhibitory effects of levcromakalim were blocked by glibenclamide but not by tetraethylammonium or iberiotoxin. Levcromakalim may reduce the Ca^<2+>-sensitivity of the contractile proteins. Thus, levcromakalim can be a candidate of therapeutic agents for delayd vasospasm after subarachnoid hemorrhage, since in the canine basilar artery levcromakalim reduces [Ca^<2+>]_i and vascular tone independently of the states of … More BK channels.The elucidation of the inhibitory of the hyperpolarization induced by K^+ chnnel openers on the Ca^<2+> movements and force of contraction produced by either the stimulation with agonists or depolarization with high KCI has shown as following : When the plasma membrane is hyperpolarized by K^+ channel openers, voltage-dependent L-type Ca^<2+> channels are deactivated and the influx of Ca^<2+> is decreased. The hyperpolarization of the plasma membrane also has another inhibitory effects on the membrane-associated enzyme activity, phospholipase C.The IP_3 production and IP_3-induced Ca^<2+> release from intracellular stores related with the stimulation of the agonist receptors are inhibited by the hyperpolarization of the plasma membrane by K^+ channel openers. The voltage-dependence of the Ca^<2+> sensitivity of contractile elements. Furthermore, membrane hyperpolarization induced by various K^+ channel openers, relaxd canine coronary arteries more profoundly than decreased [Ca^<2+>]_i.Thus, the membrane voltage may regulate intracellular enzyme activities, including contractile elements. This new facet of signal transduction therefore should be considered in the control of vascular tone. Less

通过测量细胞内Ca^<2+>浓度的变化（[Ca^<2+>] _ I），仅用CORINCINE或PORCINE CORCINARE，通过测量细胞内Ca^<2+>浓度的变化来检查大型电导率Ca^<2+> - 激活的K^+通道（BK）和ATP敏感的K^+（bk）和ATP敏感的K^+（K_ <ATP>）通道参与动脉张力调节的调节。在静止条件下，levcromagalim减少了[Ca^<2+>] _ I和音调。 levcromagalim抑制了[Ca^<2+>] _ I和收缩的5-羟色胺诱导的增加，其最大作用远大于尼古丁的效果。 Levcromagalim的抑制作用被Glibenclamide封闭，而不是被四乙基氨或Iberiotoxin阻断。 Levcromagalim可能会降低收缩蛋白的CA^<2+>。 That, levcromagalim can be a candidate of therapeutic agents for delayed vasospasm after subarachnoid hemorrhage, since in the canine basilar artery levcromagalim reduces [Ca^<2+>]_i and vascular tone independently of the states of … More BK channels.The elucidation of the inhibitory of the hyperpolarisation induced by K^+ chnnel openers on the Ca^<2+>由激动剂刺激或高KCI的沉积产生的运动和收缩力如下：当质膜被K^+通道开孔器过度渗透时，电压依赖性的L型Ca^<2+>通道被取消ca^<2 <2+> <2> <2+>> <2+>降低。质膜的超极化还对与膜相关的酶活性，磷脂酶C. C. 3和IP_3诱导的Ca^<2+>从与激动剂受体刺激相关的CA^<2+>释放的磷脂酶释放也有另一种抑制作用。收缩元件的CA^<2+>敏感性的电压依赖性。此外，与先进的[Ca^<2+>] _ i.thus相比，各种K^+通道开启器，放松的犬冠状动脉诱导的膜超极化更深刻，膜电压可能调节细胞内酶活性，包括收缩元件。因此，应在血管张力的控制中考虑信号转导的新方面。较少的

项目成果

柳澤 輝行・須貝 和幸: "K^+チャネルと血管平滑筋." 脳神経外科速報,6(8) 585-589,1996.6・8. 585-589 (1996)

Teruyuki Yanagisawa 和 Kazuyuki Sugai：“K^+ 通道和血管平滑肌。”，6(8) 585-589，1996.6/8 (1996)。

Kurosawa H,Yanagisawa T,Taira N: "Biphacic antagonisms of β-blockers against positive introgie responses via β,adorenoceptors in iselated canine right ventricular muscle." J.Cardio vasc.Pharmacol.27. 262-268 (1996)

Kurosawa H、Yanagisawa T、Taira N：“β-受体阻滞剂通过孤立的犬右心室肌肉中的 β，肾上腺素受体对正内源反应的双相拮抗作用。J.Cardio vasc.Pharmacol.262-268。”

Kensuke, ORITO,Teruyuki, YANAGISAWA & Norio, TAIRA: "A possibility that ATP-sensitive potassium channel in coronary artery] has a high-affinity internal binding site for tetraalkylammonium" Japan.J.Pharmacol. 64 (4). 297-301 (1994)

健介、织户、辉之、柳泽

Sugai K, Yanagisawa T, etal.: "Levcromakalim decreases aytopalasmic Ca^<2+>,vascular tone and Ca^<2+> sensitivity in canine basilar artery" Fund.Clim.Pharmacol. in press. (1998)

Sugai K、Yanagisawa T 等人：“Levcromakalim 降低犬基底动脉中的细胞浆细胞 Ca^<2>、血管张力和 Ca^<2> 敏感性”Fund.Clim.Pharmacol。

Yuji, OKADA,Teruyki, YANAGISAWA & Norio, TAIRA: "Membrane potential regulates the Ca^<2+> sensitivity of contractile elements in coronary arterial smooth muscle" Heart Vessels. (Suppl.9). 150-152 (1995)

雄二、冈田、照之、柳泽