Involvement of Gi protein-dependent BKCa channel activation in β2-adrenoceptor-mediated dilation of retinal arterioles in rats
Involvement of Gi protein-dependent BKCa channel activation in β2-adrenoceptor-mediated dilation of retinal arterioles in rats
复制标题
Gi 蛋白依赖性 BKCa 通道激活参与 β2 肾上腺素受体介导的大鼠视网膜小动脉扩张
DOI：
10.1007/s00210-020-01895-1
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Nakahara T
中科院分区：
文献类型：
--
作者：
Mori A;Taniai A;Hasegawa M;Sakamoto K;Nakahara T
循环儿茶酚胺有助于调节视网膜血管张力。我们之前的研究表明，大电导Ca2+激活K+(BKCa)通道的激活参与了β2-肾上腺素受体介导的大鼠视网膜小动脉扩张。本研究旨在探讨Gi蛋白在视网膜小动脉中β2-肾上腺素受体介导的BKCachannels激活中的作用。取活体大鼠眼底图像，测量视网膜小动脉直径。连续记录体表血压和心率。静脉输注福莫特罗（0.01 ~ 0.3 μg/kg/min）， β2-肾上腺素能受体激动剂，增加视网膜小动脉直径，降低平均动脉压，且呈剂量依赖性。玻璃体内注射iberiotoxin （20 pmol/眼），一种BKCachannels的抑制剂，显著减弱福莫特罗诱导的视网膜小动脉扩张。用另一种β2-肾上腺素能受体激动剂沙丁胺醇（0.03-3 μg/kg/min）代替福莫特罗，结果相似。然而，在静脉输注多巴胺（1-30 μg/kg/min， β1-肾上腺素受体激动剂）、CL316243 （0.3-10 μg/kg/min， β3-肾上腺素受体激动剂）、前列腺素I2（0.03-10 μg/kg/min，前列腺素IP受体激动剂）和福斯克林（1-10 μg/kg/min，腺苷酸环化酶激活剂）后，iberiotoxin对视网膜血管扩张剂的反应没有显著影响。玻璃体内注射百日咳毒素（66 ng/眼；一种Gi蛋白抑制剂）可显著减弱福莫特罗诱导的视网膜小动脉扩张，而非多巴胺和CL316243。在百日咳毒素存在的情况下，iberiotoxin对福莫特罗诱导的视网膜小动脉扩张无抑制作用。这些结果表明，刺激β2-肾上腺素受体通过百日咳毒素敏感的Gi蛋白依赖的bkcachanels激活来扩张视网膜小动脉。
Circulating catecholamines contribute to the regulation of retinal vascular tone. Our previous studies have demonstrated that the activation of large-conductance Ca2+-activated K+(BKCa) channels is involved in the β2-adrenoceptor-mediated dilation of retinal arterioles in rats. The present study aimed to examine the role of Gi protein in the β2-adrenoceptor-mediated activation of BKCachannels in the retinal arterioles. Images of in vivo rat ocular fundi were captured, and the diameters of retinal arterioles were measured. Systemic blood pressure and heart rate were recorded continuously. Intravenous infusion of formoterol (0.01–0.3 μg/kg/min), a β2-adrenoceptor agonist, increased the diameter of retinal arterioles but decreased mean arterial pressure in a dose-dependent manner. Intravitreal injection of iberiotoxin (20 pmol/eye), an inhibitor of BKCachannels, significantly attenuated the formoterol-induced dilation of retinal arterioles. Similar results were obtained when salbutamol (0.03–3 μg/kg/min), another β2-adrenoceptor agonist, was used instead of formoterol. However, iberiotoxin had no significant effect on retinal vasodilator responses to intravenous infusion of denopamine (1–30 μg/kg/min; a β1-adrenoceptor agonist), CL316243 (0.3–10 μg/kg/min; a β3-adrenoceptor agonist), prostaglandin I2(0.03–10 μg/kg/min; a prostanoid IP receptor agonist), and forskolin (1–10 μg/kg/min; an adenylyl cyclase activator). Intravitreal injection of pertussis toxin (66 ng/eye; a Gi protein inhibitor) significantly attenuated the dilation of retinal arterioles induced by formoterol but not by denopamine and CL316243. In the presence of pertussis toxin, iberiotoxin had no inhibitory effect on formoterol-induced dilation of retinal arterioles. These results suggest that stimulation of β2-adrenoceptors dilates retinal arterioles through pertussis toxin–sensitive Gi protein–dependent activation of BKCachannels in rats in vivo.