Role of store-operated Ca(2+) entry in adenosine-induced vasodilatation of rat small mesenteric artery.
Role of store-operated Ca(2+) entry in adenosine-induced vasodilatation of rat small mesenteric artery.
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DOI：
10.1152/ajpheart.00060.2009
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发表时间：
2009-07
期刊：
影响因子：
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通讯作者：
ShengPeng Wang;Yan Zhang;W. Wier;Xiao-Jiang Yu;Ming-Yi Zhao;Hao Hu;Lei Sun;Xi He;Youhua Wang;B. Wang;W. Zang
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文献类型：
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作者：
ShengPeng Wang;Yan Zhang;W. Wier;Xiao-Jiang Yu;Ming-Yi Zhao;Hao Hu;Lei Sun;Xi He;Youhua Wang;B. Wang;W. Zang
商店操作钙（2+）进入（SOCE）最近被提出有助于钙（2+）流入血管平滑肌细胞（VSMCs）。众所周知，腺苷通过血管舒张增加营养和氧气供应，具有抗缺氧和缺血的保护作用。本研究旨在检验SOCE在腺苷诱导的血管舒张中具有功能作用的假设。获得大鼠肠系膜小阻力动脉和肠系膜VSMCs。用灵敏的肌图系统测量离体动脉环的等距张力。用激光扫描共聚焦显微镜测定载氟3的VSMCs细胞内Ca（2+）浓度。腺苷（0.1-100微米）以浓度依赖的方式放松由苯肾上腺素预收缩的动脉环。在培养的肠系膜VSMCs中，thapsigargin的被动储存耗尽和phenylephrine的主动储存耗尽都诱导了SOCE引起的Ca（2+）内流。腺苷抑制ssoc介导的细胞内Ca（2+）水平的升高。在离体动脉环中，腺苷抑制ssoc引起的由于储存耗尽的收缩。SCH-58261对A（2A）受体的拮抗作用和SQ-22536对腺苷酸环化酶的抑制作用大大减弱了腺苷反应。cAMP类似物8-溴-cAMP模拟了腺苷对SOCE的影响。我们的研究结果表明腺苷血管舒张的新机制涉及通过cAMP信号通路调节SOCE，这是由于腺苷a （2A）受体的激活。
Store-operated Ca(2+) entry (SOCE) has recently been proposed to contribute to Ca(2+) influx in vascular smooth muscle cells (VSMCs). Adenosine is known for its protective role against hypoxia and ischemia by increasing nutrient and oxygen supply through vasodilation. This study was designed to examine the hypothesis that SOCE have a functional role in adenosine-induced vasodilation. Small mesenteric resistance arteries and mesenteric VSMCs were obtained from rats. Isometric tensions of isolated artery rings were measured by a sensitive myograph system. Laser-scanning confocal microscopy was used to determine the intracellular Ca(2+) concentration of fluo 3-loaded VSMCs. Adenosine (0.1-100 microM) relaxed artery rings that were precontracted by phenylephrine in a concentration-dependent manner. In cultured mesenteric VSMCs, passive store depletion by thapsigargin and active store depletion by phenylephrine both induced Ca(2+) influx due to SOCE. Adenosine inhibited SOCE-mediated increases in cytosolic Ca(2+) levels evoked by the emptying of the stores. In isolated artery rings, adenosine inhibited SOCE-induced contractions due to store depletion. A(2A) receptor antagonism with SCH-58261 and adenylate cyclase inhibition with SQ-22536 largely attenuated adenosine responses. The cAMP analog 8-bromo-cAMP mimicked the effects of adenosine on SOCE. Our results indicate a novel mechanism of vasodilatation by adenosine that involves regulation of SOCE through the cAMP signaling pathway due to activation of adenosine A(2A) receptors.