首页> 外文期刊>The Journal of Membrane Biology: An International Journal for Studies on the Structure, Function & Genesis of Biomembranes >Differential desensitization of Ca2+ mobilization and vasoconstriction by ET(A) receptors in the gerbil spiral modiolar artery.
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Differential desensitization of Ca2+ mobilization and vasoconstriction by ET(A) receptors in the gerbil spiral modiolar artery.

机译:Ca2 +动员和ET(A)受体在沙鼠螺旋mod动脉中的差异收缩脱敏和血管收缩。

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Endothelins are known to be among the most potent endogenous vasoconstrictors. Vasoconstriction of the spiral modiolar artery, which supplies the cochlea, may be implicated in hearing loss and tinnitus. The purpose of the present study was to determine whether the spiral modiolar artery responds to endothelin, whether a change in the cytosolic Ca2+ concentration ([Ca2+]i) mediates the response and which endothelin receptors are present. The vascular diameter and [Ca2+]i were measured simultaneously by videomicroscopy and microfluorometry in the isolated spiral modiolar artery from the gerbil. ET-1 induced a transient [Ca2+]i increase and a strong and long-lasting vasoconstriction. The transient [Ca2+]i increase underwent rapid desensitization, was independent of extracellular Ca2+ and inhibited by the IP3-receptor blocker (75 microm) 2-aminoethoxydiphenyl borate (2-APB) and by depletion of Ca2+ stores with 10(-6) m thapsigargin. In contrast, the vasoconstriction displayed no comparable desensitization. The initial vasoconstriction was independent of extracellular Ca2+ but maintenance of the constriction depended on the presence of extracellular Ca2+. The half-maximal concentration values (EC50) for the agonists ET-1, ET-3 and sarafotoxin S6c were 0.8 nm, >10 nm and >100 nm, respectively. Affinity constants for the antagonists BQ-123 and BQ-788 were 24 nm and 77 nm, respectively. These observations demonstrate that ET-1 mediates a vasoconstriction of the gerbil spiral modiolar artery via ETA receptors and an IP3 receptor-mediated release of Ca2+ from thapsigargin-sensitive Ca2+ stores. The marked difference in desensitization between Ca2+ mobilization and vasoconstriction suggests that Ca2+ mobilization is not solely responsible for the vasoconstriction and that other signaling mechanisms must be present.
机译:内皮素已知是最有效的内源性血管收缩药。供应耳蜗的螺旋mod动脉的血管收缩可能与听力下降和耳鸣有关。本研究的目的是确定螺旋mod毛动脉是否对内皮素有反应,胞浆中Ca2 +浓度([Ca2 +] i)的变化是否介导了该反应以及存在哪些内皮素受体。通过视频显微镜和微荧光法同时测量了从沙鼠中分离出的螺旋mod动脉中的血管直径和[Ca2 +] i。 ET-1引起短暂的[Ca2 +] i升高以及强烈而持久的血管收缩。瞬态[Ca2 +] i的增加经历了快速脱敏,与细胞外Ca2 +无关,并受到IP3-受体阻滞剂(75 microm)2-氨基乙氧基二苯基硼酸酯(2-APB)的抑制,以及被Ca2 +的10(-6)m耗尽所抑制毒胡萝卜素。相反,血管收缩没有表现出可比的脱敏。最初的血管收缩与细胞外Ca2 +无关,但收缩的维持取决于细胞外Ca2 +的存在。激动剂ET-1,ET-3和sarafotoxin S6c的半数最大浓度值(EC50)分别为0.8 nm,> 10 nm和> 100 nm。拮抗剂BQ-123和BQ-788的亲和常数分别为24 nm和77 nm。这些观察结果表明,ET-1通过ETA受体介导了沙鼠螺旋mod动脉的血管收缩,并通过IP3受体介导了毒胡萝卜素敏感的Ca2 +储存体释放Ca2 +。 Ca2 +动员和血管收缩之间脱敏的显着差异表明,Ca2 +动员不仅是血管收缩的唯一原因,而且还必须存在其他信号传导机制。

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