Overexpression of bradykinin type 2 receptors on glioma cells enhances bradykinin-mediated blood-brain tumor barrier permeability increase.
Variations in the expression levels of bradykinin (BK) type 2 receptors (B2R) in different brain tumors may explain variable increases in BK-mediated blood-brain tumor barrier (BTB) permeability. This study investigated whether elevation of the B2R expression levels on glioma cells enhances BK-mediated BTB permeability increases. Stable transfectants of C6 rat glioma cells overexpressing B2R were established by transfection with recombinant vectors harboring rat B2R cDNA sequence. Elevated B2R expression levels in transfectants were confirmed by quantitative real-time PCR, Western blots, and [3H]-BK binding studies. BTB permeability was quantified with autoradiography and expressed as a unidirectional transport constant, Ki, for [14C]-alpha-aminoisobutyric acid (AIB: Mr 103), using a rat brain tumor model. Baseline Ki values in tumors overexpressing B2R were not significantly higher than in control tumors. Ki values after BK treatment in tumors overexpressing B2R, however, were significantly higher than in control tumors. Western blots confirmed that B2R expression levels in vivo in tumors overexpressing B2R remained higher than in control tumors. These results suggested that alteration of B2R expression levels on tumor cells could modulate BK-mediated BTB permeability. Therefore, B2R expression levels in human glioma could be used to analyze the treatment results of patients undergoing treatment involving BK-modulated BTB permeability.
Uchida
Mikito
M
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8631 West Third Street, Suite 800E, Los Angeles, CA 90048, USA.
Chen
Zutang
Z
Liu
Yunhui
Y
Black
Keith L
KL
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000235:genetics*; D001920:Bradykinin / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D001920:Bradykinin