Tissue plasminogen activator (0.01-30 mug/ml) dose-dependently inhibited th
e functional activity of P-glycoprotein, assessed by rhodamine 123 accumula
tion in GP8 immortalized rat brain endothelial cells, but this effect was u
nrelated to its proteolytic activity. Elevation of intra-endothelial cyclic
AMP concentration and stimulation of protein kinase C increased P-glycopro
tein activity in GP8 cells and also attenuated the tissue plasminogen activ
ator-induced inhibition. (C) 2001 Elsevier Science B.V. All rights reserved
.