Signal transduction and glial cell modulation of cultured brain microvessel endothelial cell tight junctions
Raub, T.J.
American Journal of Physiology 271(2 Pt 1): C495-C503
1996
ISSN/ISBN: 0002-9513 PMID: 8769988 Document Number: 457036
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.