Glycine Receptor α2 Mediates Vasodilation via Endothelial eNOS Signaling
Xueya Bai, Yan Wang, Wenying Zhou, Yueqi Yu, Yan Dai, Jinhao Li, Qinghua Chen, Wei Hou, Xiqi Zhu, Hui Bai, Qing Yang, Bin Jiang, Jingjing Ben, Hanwen Zhang, Xiaoyu Li, Chao Lu, Xiaolin Miao, Jian Xu, Nan Jiang, Juejin Wang, Steven Y. Cheng, Xudong Zhu, Qi ChenBACKGROUND:
Endothelium-derived NO is an important vasodilator essential for maintaining vascular homeostasis. However, how eNOS (endothelial nitric oxide synthase) is regulated in hypertension conditions is not yet fully understood. In this study, we describe a critical role of the GLRA2 (α2 subunit of glycine receptor) in modulating eNOS signaling and blood pressure regulation.
METHODS:
Endothelial-specific
RESULTS:
We first demonstrated selective expression of GLRA2 in arterial endothelial cells. Activation of GLRA2 by its ligand, glycine, effectively counteracts hypertension in a GLRA2-dependent manner. Our patient study indicated a negative correlation between plasma levels of glycine and blood pressure. Furthermore, we showed that endothelial GLRA2 regulates vasodilation by promoting NO production, rather than functioning solely as a chloride channel. Mechanistically, GLRA2 facilitates the phosphorylation of glycogen synthase kinase-3β at Ser9, which activates the AKT/eNOS signaling pathway in the endothelium, leading to increased NO release.
CONCLUSIONS:
This study discovers that a novel endothelial GLRA2 pathway holds significant potential for developing new strategies to control hypertension.