The molecular mechanism of dexamethasone-mediated effect on the blood-brain tumor barrier permeability in a rat brain tumor model.
This study was performed to determine whether dexamethasone (DEX) had an effect on calcium-activated potassium channels (K(Ca) channels) and Occludin protein in blood-brain tumor barrier (BTB). Using a rat brain glioma model, we found that the expression of K(Ca) channels protein and Occludin protein was significantly increased in brain tumor tissue after DEX treatment for 3 days. Compared with non-DEX-treated animals, Evans Blue levels were greatly attenuated in DEX-treated animals. These effects were significantly reversed by the glucocorticoid receptor antagonist RU38486. In addition, DEX treatment enhanced the density of I(KCa) in the rat brain microvascular endothelial cells (RBMECs) in vitro BTB. All of these results strongly suggest that DEX could be involved in the regulation of both transcellular and paracellular pathway.
Gu
Yan-Ting
YT
Department of Physiology, Institution of Life Science and Biology Pharmacopedia, Shenyang Pharmaceutical University, Culture Road no 103, Shenhe District, Shenyang 110016, Liaoning Province, PR China. yantinggu008@yahoo.com.cn
Qin
Li-Juan
LJ
Qin
Xin
X
Xu
Feng
F
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001932:Brain Neoplasms / Q000150:complications*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005070:Evans Blue; D005260:Female; D007202:Indicators and Reagents; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D062793:Occludin; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D007202:Indicators and Reagents; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D005070:Evans Blue; D003907:Dexamethasone