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Tissue plasminogen activator inhibits P-glycoprotein activity in brain endothelial cells
M A Deli1, C S Abrahám, H Takahata
1Department of Pharmacology 1, Nagasaki University School of Medicine, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan. deli-ngs@umin.ac.jp
European Journal of Pharmacology
|January 4, 2001
Abstract:
Tissue plasminogen activator (0.01-30 microgram/ml) dose-dependently inhibited the functional activity of P-glycoprotein, assessed by rhodamine 123 accumulation in GP8 immortalized rat brain endothelial cells, but this effect was unrelated to its proteolytic activity. Elevation of intra-endothelial cyclic AMP concentration and stimulation of protein kinase C increased P-glycoprotein activity in GP8 cells and also attenuated the tissue plasminogen activator-induced inhibition.