TY - JOUR
T1 - β2- but not β1-adrenoceptor activation modulates intracellular oxygen availability
AU - Li, Jun
AU - Yan, Biao
AU - Huo, Zhaoxia
AU - Liu, Ying
AU - Xu, Jiahong
AU - Sun, Yunfu
AU - Liu, Yi
AU - Liang, Dandan
AU - Peng, Luying
AU - Zhang, Youyi
AU - Zhou, Zhao Nian
AU - Shi, Jingyi
AU - Cui, Jianmin
AU - Chen, Yi Han
PY - 2010/8/15
Y1 - 2010/8/15
N2 - β-Adrenoceptors (β-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 β-AR activation can modulate intracellular oxygen. Here we used mitochondrial and cytosolic target Renilla luciferase to detect intracellular oxygen concentration. Pharmacological experiments revealed that β2-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 β2-AR-Gi-eNOS pathway is involved in this regulation. β2-AR activation increased the AMP/ATP ratio, AMPK activity, ROS production and prolyl hydroxylase activity. These effects also contribute to the regulation of β2-AR signalling, thus providing an additional layer of complexity to enforce the specificity of β1-AR and β2-AR signalling. Collectively, the study provides novel insight into the modulation of oxygen homeostasis, broadens the scope of β2-AR function, and may have crucial implications for β2-AR signalling regulation.
AB - β-Adrenoceptors (β-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 β-AR activation can modulate intracellular oxygen. Here we used mitochondrial and cytosolic target Renilla luciferase to detect intracellular oxygen concentration. Pharmacological experiments revealed that β2-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 β2-AR-Gi-eNOS pathway is involved in this regulation. β2-AR activation increased the AMP/ATP ratio, AMPK activity, ROS production and prolyl hydroxylase activity. These effects also contribute to the regulation of β2-AR signalling, thus providing an additional layer of complexity to enforce the specificity of β1-AR and β2-AR signalling. Collectively, the study provides novel insight into the modulation of oxygen homeostasis, broadens the scope of β2-AR function, and may have crucial implications for β2-AR signalling regulation.
UR - http://www.scopus.com/inward/record.url?scp=77955720593&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2010.190900
DO - 10.1113/jphysiol.2010.190900
M3 - Article
C2 - 20547682
AN - SCOPUS:77955720593
SN - 0022-3751
VL - 588
SP - 2987
EP - 2998
JO - Journal of Physiology
JF - Journal of Physiology
IS - 16
ER -