adenosine-5--phosphorothioate and Glioma

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.

Topics: Adenosine Monophosphate; Analysis of Variance; Animals; Antineoplastic Agents, Hormonal; Blood-Brain Barrier; Bradykinin; Brain Neoplasms; Cell Line, Tumor; Dexamethasone; Disease Models, Animal; Drug Interactions; Female; Glioma; Membrane Potentials; Patch-Clamp Techniques; Permeability; Potassium Channels, Inwardly Rectifying; Rats; Rats, Wistar; Thionucleotides; Xenograft Model Antitumor Assays