화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.498, No.4, 795-802, 2018
Adenosine A(2A) receptor inhibition restores the normal transport of endothelial glutamate transporters in the brain
Excitatory amino acid transporters (EAATs) on cerebral vascular endothelial cells play an important role in maintaining glutamate homeostasis in the brain. The dysfunction of endothelial EAATs is an important reason for the dramatically elevated brain glutamate levels after brain injury, such as traumatic brain injury (TBI). The adenosine A(2A) receptor (A(2A)R) plays an important role in regulating the brain glutamate level after brain injury; however, researchers have not clearly determined whether this role was related to its ability to regulate endothelial EAATs. Activation of A(2A)R in vitro not only decreased the PKA- and glutamate level-dependent strengthening of the interaction between NKA-alpha 1 and the FXYD1 subunit and the subsequent decrease in the activity of Na+/K+-ATPases (NKAs) but also enhanced its interaction with EAATs and ultimately aggravated the reverse transport function of endothelial EAATs under oxygen glucose deprivation (OGD) conditions. Conversely, inhibition of A(2A)R restored the normal transport of EAAT. Moreover, A(2A)R inhibition increased NKA activity and decreased its interaction with EAATs in isolated brain capillaries after TBI, further confirming its role in endothelial EAATs in vivo. Based on our results, A(2A)R played an important role in regulating endothelial EAAT function, and strategies that restore the normal transport of endothelial EAATs through the inhibition of A(2A)R might serve as an effective treatment for brain injury. (C) 2018 Elsevier Inc. All rights reserved.