Dexamethasone enhances adenosine 5'-triphosphate-sensitive potassium channel expression in the blood-brain tumor barrier in a rat brain tumor model.
This study was performed to determine whether dexamethasone (DEX) had an effect on ATP-sensitive potassium channels (K(ATP) channels) in blood-brain tumor barrier (BTB). Using a rat brain glioma model, we found that DEX could significantly increase the expression of K(ATP) channels protein at tumor sites. And bradykinin-induced increase of K(ATP) channels protein was further enhanced after DEX pretreatment for 3 consecutive days via Western blots and immunohistochemistry methods. In addition, DEX pretreatment enhanced bradykinin-mediated increase of the density of I(KATP) in the cultured rat C6 glioma cells using the patch-clamp technique in a whole-cell configuration. DEX significantly decreased the BTB permeability, but it did not reduce bradykinin-mediated BTB permeability increase, which were significantly attenuated by the K(ATP) channel antagonist glibenclamide. This led to the conclusion that DEX-mediated change in BTB permeability is, at least partly, due to accelerated formation of K(ATP) channel, an important target in the biochemical regulation of this process.
Gu
Yan-Ting
YT
Department of Neurobiology, College Basic of Medicine, China Medical University, Shenyang, 110001, Liaoning Province, PR China.
Zhang
Hua
H
Xue
Yi-Xue
YX
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D010539:Permeability / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000099161:Kcnj11 Channel
D000249:Adenosine Monophosphate; D018931:Antineoplastic Agents, Hormonal; D001920:Bradykinin; D003907:Dexamethasone; D024661:Potassium Channels, Inwardly Rectifying; D013873:Thionucleotides; D000099161:Kcnj11 Channel; C014308:adenosine 5'-phosphorothioate