β2- but not β1-adrenoceptor activation modulates intracellular oxygen availability
β2- but not β1-adrenoceptor activation modulates intracellular oxygen availability
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DOI：
10.1113/jphysiol.2010.190900
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发表时间：
2010-08-15
影响因子：
5.5
通讯作者：
Chen, Yi-Han
中科院分区：
文献类型：
--
作者：
Li, Jun;Yan, Biao;Chen, Yi-Han
β-肾上腺素受体（β-AR）在心血管功能的调节中起着关键作用。细胞内氧稳态对心肌细胞的存活至关重要。然而，目前还不清楚β-AR激活是否可以调节细胞内氧。在这里，我们使用线粒体和胞质靶海肾荧光素酶来检测细胞内氧浓度。药理学实验表明，β（2）-AR激活特异性调节心肌细胞和COS 7细胞中的细胞内氧。抑制性G蛋白（G（i））抑制、内皮型一氧化氮合酶（eNOS）阻断和NO清除可消除这种作用，表明β（2）-AR-G（i）-eNOS通路参与了这种调节。β（2）-AR激活增加AMP/ATP比值、AMPK活性、ROS产生和脯氨酰羟化酶活性。这些作用也有助于β（2）-AR信号的调节，从而提供了额外的复杂性层，以加强β（1）-AR和β（2）-AR信号的特异性。总的来说，这项研究为氧稳态的调节提供了新的见解，拓宽了β（2）-AR功能的范围，并可能对β（2）-AR信号调节产生重要影响。
beta-Adrenoceptors (beta-ARs) play a critical role in the regulation of cardiovascular function. Intracellular oxygen homeostasis is crucial for the survival of cardiomyocytes. However, it is still unclear whether beta-AR activation can modulate intracellular oxygen. Here we used mitochondrial and cytosolic target Renilla luciferase to detect intracellular oxygen concentration. Pharmacological experiments revealed that beta(2)-AR activation specifically regulates intracellular oxygen in cardiomyocytes and COS7 cells. This effect was abrogated by inhibitory G protein (G(i)) inhibition, endothelial nitric oxide synthase (eNOS) blockade, and NO scavenging, implicating that the beta(2)-AR-G(i)-eNOS pathway is involved in this regulation. beta(2)-AR activation increased the AMP/ATP ratio, AMPK activity, ROS production and prolyl hydroxylase activity. These effects also contribute to the regulation of beta(2)-AR signalling, thus providing an additional layer of complexity to enforce the specificity of beta(1)-AR and beta(2)-AR signalling. Collectively, the study provides novel insight into the modulation of oxygen homeostasis, broadens the scope of beta(2)-AR function, and may have crucial implications for beta(2)-AR signalling regulation.