Dexamethasone enhances adenosine 5′-triphosphate-sensitive potassium channel expression in the blood–brain tumor barrier in a rat brain tumor model

• Published in: Brain research Vol. 1162; pp. 1 - 8
• Main Authors: Gu, Yan-ting, Zhang, Hua, Xue, Yi-xue
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 08.08.2007; Amsterdam Elsevier; New York, NY
• Subjects: Adenosine Monophosphate - analogs & derivatives; Adenosine Monophosphate - pharmacology; Analysis of Variance; Animals; Antineoplastic Agents, Hormonal - pharmacology; ATP-sensitive potassium channel; Biological and medical sciences; Blood-Brain Barrier - drug effects; Blood-tumor barrier; Blood–brain barrier; Bradykinin; Bradykinin - pharmacology; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain Neoplasms - secondary; Cell Line, Tumor; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Dexamethasone; Dexamethasone - pharmacology; Disease Models, Animal; Drug Interactions; Female; Fundamental and applied biological sciences. Psychology; Glioma; Glioma - metabolism; Glioma - pathology; Glioma - secondary; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Neurology; Patch-Clamp Techniques; Permeability - drug effects; Potassium Channels, Inwardly Rectifying - agonists; Potassium Channels, Inwardly Rectifying - antagonists & inhibitors; Potassium Channels, Inwardly Rectifying - metabolism; Rats; Rats, Wistar; Thionucleotides - pharmacology; Tumors of the nervous system. Phacomatoses; Vertebrates: nervous system and sense organs; Xenograft Model Antitumor Assays; Dexamethasone; Glioma; Bradykinin; Blood-tumor barrier; Blood–brain barrier; ATP-sensitive potassium channel; Animal model; Glial cell; Rat; Neuroglia; Rodentia; Central nervous system; Dexamethasone,Bradykinin,Blood-tumor barrier,Blood-brain barrier,ATP-sensitive potassium channel,Glioma; Ionic channel; Neuropeptide; Blood brain barrier; Encephalon; Vertebrata; Mammalia; Animal; Tumor; ATP; Potassium
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.05.053

Abstract This study was performed to determine whether dexamethasone (DEX) had an effect on ATP-sensitive potassium channels ( KATP channels) in blood–brain tumor barrier (BTB). Using a rat brain glioma model, we found that DEX could significantly increase the expression of KATP channels protein at tumor sites. And bradykinin-induced increase of KATP 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 IKATP 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 KATP channel antagonist glibenclamide. This led to the conclusion that DEX-mediated change in BTB permeability is, at least partly, due to accelerated formation of KATP channel, an important target in the biochemical regulation of this process.