Tissue plasminogen activator inhibits P-glycoprotein activity in brain endothelial cells

M A Deli; C S Abrahám; H Takahata; M Niwa

doi:10.1016/s0014-2999(00)00895-5

Tissue plasminogen activator inhibits P-glycoprotein activity in brain endothelial cells

Eur J Pharmacol. 2001 Jan 5;411(1-2):R3-R5. doi: 10.1016/s0014-2999(00)00895-5.

Authors

M A Deli¹, C S Abrahám, H Takahata, M Niwa

Affiliation

¹ Department of Pharmacology 1, Nagasaki University School of Medicine, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan. deli-ngs@umin.ac.jp

PMID: 11137878
DOI: 10.1016/s0014-2999(00)00895-5

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / drug effects*
ATP Binding Cassette Transporter, Subfamily B / metabolism
Animals
Blood-Brain Barrier
Brain / cytology
Brain / metabolism
Cell Line, Transformed
Dose-Response Relationship, Drug
Endothelium, Vascular / cytology
Endothelium, Vascular / drug effects*
Endothelium, Vascular / metabolism
Rhodamine 123 / metabolism
Tissue Plasminogen Activator / pharmacology*

Substances

ATP Binding Cassette Transporter, Subfamily B
Rhodamine 123
Tissue Plasminogen Activator