Prostacyclin receptor-mediated ATP release from erythrocytes requires the voltage-dependent anion channel
Prostacyclin receptor-mediated ATP release from erythrocytes requires the voltage-dependent anion channel
复制标题
DOI：
10.1152/ajpheart.00998.2011
复制
发表时间：
2012-02-01
影响因子：
4.8
通讯作者：
Sprague, Randy S.
中科院分区：
文献类型：
--
作者：
Sridharan, Meera;Bowles, Elizabeth A.;Sprague, Randy S.
首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容前列环素受体介导的红细胞ATP释放需要电压依赖的阴离子通道。Am J Physiol心脏圈Physiol 302：H553-H559,2012。首次发表于2011年12月9日；doi：10.1152/ajpheart.00998.2011。-红细胞因其对局部生理和药物刺激的反应而释放血管扩张剂三磷酸腺苷的能力而被认为是血管口径的控制器。调节红细胞三磷酸腺苷的释放需要激活涉及G蛋白(G(I)或G(S))、腺苷环化酶、蛋白激酶A、囊性纤维化跨膜电导调节因子的信号通路，以及这种高电荷阴离子离开细胞的最终通道。虽然PAnnexin 1已被证明是人红细胞在氧分压降低时释放ATP的最终通道，但它并不参与这些细胞中前列环素(IP)受体刺激后的ATP运输，这表明必须有额外的蛋白质参与。利用针对电压依赖阴离子通道(VDAC)1的抗体，我们证实该蛋白存在于人红细胞膜上。为了研究VDAC在ATP释放中的作用，使用了两种结构不同的VDAC抑制剂：Bclx(L)BH4(4-23)和TRO19622。作为对IP受体激动剂iloprost和UT-15C的反应，这两种VDAC抑制剂都能抑制ATP的释放，但对iloprost诱导的cAMP积聚和细胞内总的ATP浓度都没有影响。综上所述，这些发现支持VDAC是人红细胞IP受体介导的信号通路中的ATP管道的假设。此外，β-肾上腺素能受体激动剂异丙肾上腺素与红细胞孵育后，β-肾上腺素能受体激动剂异丙肾上腺素对红细胞三磷酸腺苷的释放无抑制作用，但β-肾上腺素能受体激动剂异丙肾上腺素对红细胞三磷酸腺苷的释放有抑制作用，提示人红细胞存在另一种三磷酸腺苷释放通道。
Sridharan M, Bowles EA, Richards JP, Krantic M, Davis KL, Dietrich KA, Stephenson AH, Ellsworth ML, Sprague RS. Prostacyclin receptor-mediated ATP release from erythrocytes requires the voltage-dependent anion channel. Am J Physiol Heart Circ Physiol 302: H553-H559, 2012. First published December 9, 2011; doi:10.1152/ajpheart.00998.2011.-Erythrocytes have been implicated as controllers of vascular caliber by virtue of their ability to release the vasodilator ATP in response to local physiological and pharmacological stimuli. The regulated release of ATP from erythrocytes requires activation of a signaling pathway involving G proteins (G(i) or G(s)), adenylyl cyclase, protein kinase A, and the cystic fibrosis transmembrane conductance regulator as well as a final conduit through which this highly charged anion exits the cell. Although pannexin 1 has been shown to be the final conduit for ATP release from human erythrocytes in response to reduced oxygen tension, it does not participate in transport of ATP following stimulation of the prostacyclin (IP) receptor in these cells, which suggests that an additional protein must be involved. Using antibodies directed against voltage-dependent anion channel (VDAC)1, we confirm that this protein is present in human erythrocyte membranes. To address the role of VDAC in ATP release, two structurally dissimilar VDAC inhibitors, Bcl-x(L) BH4(4-23) and TRO19622, were used. In response to the IP receptor agonists, iloprost and UT-15C, ATP release was inhibited by both VDAC inhibitors although neither iloprost-induced cAMP accumulation nor total intracellular ATP concentration were altered. Together, these findings support the hypothesis that VDAC is the ATP conduit in the IP receptor-mediated signaling pathway in human erythrocytes. In addition, neither the pannexin inhibitor carbenoxolone nor Bcl-x(L) BH4(4-23) attenuated ATP release in response to incubation of erythrocytes with the beta-adrenergic receptor agonist isoproterenol, suggesting the presence of yet another channel for ATP release from human erythrocytes.