Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China.
J Physiol. 2010 Aug 15;588(Pt 16):2987-98. doi: 10.1113/jphysiol.2010.190900. Epub 2010 Jun 14.
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 beta2-AR activation specifically regulates intracellular oxygen in cardiomyocytes and COS7 cells. This effect was abrogated by inhibitory G protein (Gi) inhibition, endothelial nitric oxide synthase (eNOS) blockade, and NO scavenging, implicating that the beta2-AR-Gi-eNOS pathway is involved in this regulation. beta2-AR activation increased the AMP/ATP ratio, AMPK activity, ROS production and prolyl hydroxylase activity. These effects also contribute to the regulation of beta2-AR signalling, thus providing an additional layer of complexity to enforce the specificity of beta1-AR and beta2-AR signalling. Collectively, the study provides novel insight into the modulation of oxygen homeostasis, broadens the scope of beta2-AR function, and may have crucial implications for beta2-AR signalling regulation.
β-肾上腺素受体（β-AR）在心血管功能调节中起着关键作用。细胞内氧稳态对于心肌细胞的存活至关重要。然而，β-AR 激活是否能调节细胞内氧还不清楚。在这里，我们使用线粒体和细胞质靶标 Renilla 荧光素酶来检测细胞内氧浓度。药理实验表明，β2-AR 激活特异性调节心肌细胞和 COS7 细胞内的氧。这种作用被抑制性 G 蛋白（Gi）抑制、内皮型一氧化氮合酶（eNOS）阻断和 NO 清除所阻断，表明β2-AR-Gi-eNOS 途径参与了这种调节。β2-AR 激活增加了 AMP/ATP 比、AMPK 活性、ROS 产生和脯氨酰羟化酶活性。这些效应也有助于β2-AR 信号的调节，从而为β1-AR 和β2-AR 信号的特异性提供了额外的复杂性。总之，该研究为氧稳态的调节提供了新的见解，拓宽了β2-AR 功能的范围，并可能对β2-AR 信号调节具有重要意义。
