Tissue plasminogen activator inhibits P-glycoprotein activity in brain endothelial cells.
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.
Deli
M A
MA
Department of Pharmacology 1, Nagasaki University School of Medicine, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan. deli-ngs@umin.ac.jp
Abrahám
C S
CS
Takahata
H
H
Niwa
M
M
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020112:Rhodamine 123 / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D018435:ATP Binding Cassette Transporter, Subfamily B; D020112:Rhodamine 123; D010959:Tissue Plasminogen Activator