Signal transduction and glial cell modulation of cultured brain
microvessel endothelial cell tight junctions.
Raub, Thomas J.
Drug Delivery Systems Research, Pharmacia & Upjohn, Inc., 301
Henrietta Street, Kalamazoo, MI 49007
APStracts 3:0043C, 1996.
Non-contact co-culture of post-confluent, bovine brain microvessel
endothelial cells (BMEC) monolayers with rat C6 glioma cells results
in markedly decreased transmonolayer permeability measured by
electrical resistance (TER) and solute flux. An elevation in cAMP in
response to forskolin correlates with an increase in TER through a
threshold event; however, unlike forskolin the several fold increase
in TER induced by C6 cells is cAMP-independent. Activation of protein
kinase C (PKC) enhances the C6 cell-induced increase in TER and PKC
inhibition blocked C6-cell induction. Treatment of control or C6
cell-induced BMEC monolayers with pertussis toxin immediately and
irreversibly obliterates TER, without an apparent change in cyclic
GMP 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.
Received 19 September 1995; accepted in final form 25 January
1995.
APS Manuscript Number C560-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96