ETA receptors in the gerbil spiral modiolar artery.
ETA receptors in the gerbil spiral modiolar artery.
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沙鼠螺旋蜗轴动脉中的 ETA 受体。
DOI：
10.1159/000059236
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发表时间：
2002
影响因子：
--
通讯作者：
Wangemann,Philine
中科院分区：
文献类型：
--
作者：
Scherer,EliasQ;Wangemann,Philine
供应耳蜗的螺旋动脉(SMA)的血流量减少与听力损失和耳鸣有关。内皮素被认为是最有效的内源性血管收缩药。本研究的目的是确定SMA是否对内皮素有反应，存在哪种受体类型，以及涉及哪种信号转导途径。通过显微解剖从沙土鼠耳蜗处分离出SMA，并将其保存在倒置显微镜台上的浴缸中。用视频显微镜测量血管直径，用Fluo-4荧光显微镜同时监测细胞内钙离子浓度。ET-1和ET-3引起剂量依赖性的血管收缩，ET-1是更有效的激动剂。激动剂沙拉夫毒素Sóc无明显作用。优势ETA受体拮抗剂BQ123比优势ETB受体拮抗剂BQ788对ET-1引起的血管收缩具有更高的亲和力。U73122抑制磷脂酶C可抑制ET-1的血管收缩作用。用2-氨基乙氧基二苯硼酸酯阻断肌浆网上的三磷酸肌醇(IP3)受体，阻断肌浆网钙库，用thapsigargin抑制肌浆钙-ATPase，可抑制ET-1诱导的细胞内钙升高，降低ET-1诱导的血管收缩。这些结果表明，内皮素引起SMA的血管收缩，这种收缩是通过ETA受体介导的。结果提示，ETA受体的信号转导途径涉及磷脂酶C、IP3受体和thapsigargin敏感的钙库中钙离子的释放。
A reduction of blood flow in the spiral modiolar artery (SMA), which supplies the cochlea, is implicated in hearing loss and tinnitus. Endothelins are known to be the most potent endogenous vasoconstrictors. The purpose of the present study was to determine whether the SMA responds to endothelin, which receptor type is present and which signal transduction pathway is involved. The SMA was isolated from the gerbil cochlea by microdissection and superfused in a bath chamber on the stage of an inverted microscope. The vascu-lar diameter was measured by video microscopy, and the cytosolic Ca2+ concentration was monitored simultaneously by fluo-4 fluorescence microscopy. ET-1 and ET-3 caused a dosedependent vasoconstriction with ET-1 being the more potent agonist. The agonist sarafotoxin Sóc had no significant effect. The preferential ETA receptor antagonist BQ123 had a higher affinity inhibiting the ET-1-induced vasoconstriction than the preferential ETB receptor antagonist BQ788. The ET-1-induced vasoconstriction was prevented by inhibition of phospholipase C with U73122. Blockade of the inositol 1, 4, 5-trisphosphate (IP3) receptor on the sarcoplasmic reticulum Ca2+ stores with 2-aminoethoxydiphenyl borate and depletion of Ca2+ stores by inhibition of the sarcoplasmic Ca2+-ATPase with thapsigargin prevented ET-1-induced cytosolic Ca2+ increase and reduced the ET-1-induced vasoconstriction. These results demonstrate that endothelin causes a vasoconstriction of the SMA, which is mediated via ETA receptors. The data suggest that the signal transduction pathway of the ETA receptor involves phospholipase C, IP3 receptors and release of Ca²+ from thapsigargin-sensitive Ca2+ stores.