The kinin B-1 receptor is an inducible receptor expressed in response to in
flammatory mediators. We sought to determine whether kinin B-1 receptor can
be expressed on human brain endothelial cells (HBECs) in vitro and whether
signaling via this receptor can regulate permeability and chemokine produc
tion properties of these cells. Multiplex RT-PCR amplification and western
blot techniques were used to evaluate B-1 receptor expression by HBECs. Alt
hough B-1 receptor mRNA and protein could not be detected on resting HBECs,
interferon-gamma induced a dose- and time-dependent up-regulation of B-1 r
eceptor mRNA and protein on HBECs. Stimulation of interferon-gamma-treated
HBECs with the selective B-1 agonist R-838 (Sar [D-Phe(8)] des Arg(9)-BK) i
nduced a dose- and time-dependent increase in the production of inositol 3,
4,5 tri-phosphate and nitric oxide. Permeability of the HBECs monolayer, as
measured by BSA diffusion, was significantly increased by application of t
he B-1 agonist. This biological effect of R-838 could be prevented by R-715
, a B-1 receptor antagonist and by L-NAME, a nitric oxide synthase blocker.
R-838 also inhibited interleukin-8 release from HBECs. We demonstrate that
B-1 receptors can be up regulated on the surface of KBECs by molecules rel
eased during inflammatory response and that signaling via this receptor can
regulate BBB permeability and chemokine production in vitro.