Signal transduction and glial cell modulation of cultured brain microvessel endothelial cell tight junctions

被引:42
作者
Raub, TJ
机构
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 1996年 / 271卷 / 02期
关键词
astrocytes; blood-brain barrier; paracellular pathway; permeability;
D O I
10.1152/ajpcell.1996.271.2.C495
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Noncontact coculture of postconfluent bovine brain microvessel endothelial cell (BMEC) monolayers with rat C-6 glioma cells results in markedly decreased transmonolayer permeability measured by transendothelial electrical resistance (TER) and solute flux. An elevation in adenosine 3',5'-cyclic monophosphate (cAMP) in response to forskolin correlates with an increase in TER through a threshold event; however, unlike forskolin, the severalfold increase in TER induced by C-6 cells is cAMP independent. Activation of protein kinase C (PKC) enhances the C-6 cell-induced increase in TER, and PKC inhibition blocks C-6 cell induction. Treatment of control or C-6 cell-induced BMEC monolayers with pertussis toxin immediately and irreversibly obliterates TER, without an apparent change in guanosine 3',5'-cyclic monophosphate levels or viability, indicating the importance of a G protein-mediated event. A similar effect is observed with transforming growth factor-beta 1, and both responses are polarized, since the loss in TER is significantly faster in BMEC monolayers exposed basolaterally. These results suggest that astroglia modulate the blood-brain barrier through a cAMP-independent PKC-dependent pathway maintained by a G protein-coupled mechanism.
引用
收藏
页码:C495 / C503
页数:9
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