Expression of multidrug resistance-associated protein (MRP) in brain microvessel endothelial cells

Han Huai-Yun, David T. Secrest, Karen S. Mark, Debra Carney, Christine Brandquist, William F. Elmquist, Donald W. Miller

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179 Scopus citations

Abstract

Multidrug resistance-associated protein (MRP) is a recently identified drug efflux transport system that actively transports organic acids and selected glucuronide or glutathione conjugates out of the cell. The current study presents, for the first time, both functional and biochemical data demonstrating the presence of MRP in the brain microvessel endothelial cells that form the blood-brain barrier (BBB). Using known MRP inhibitors, such as indomethacin and probenecid, fluorescein accumulation in primary cultured bovine brain microvessel endothelial cell (BBMEC) monolayers was significantly enhanced compared to control. The specificity of the MRP inhibitors on cellular fluorescein accumulation was confirmed using both MRP positive (Panc-1) and MRP negative (KBv) cell lines. Furthermore, western blot analysis using a specific antibody for MRP (MRPm6) and RT-PCR studies using a complementary sequence probe for human MRP demonstrate the expression of MRP in BBMEC. Previous studies have demonstrated the significance of the P-glycoprotein drug efflux transporter in the BBB. Given its function as a drug efflux transport system, it is anticipated that MRP in the BBB will also have an important role in limiting the exposure of the brain to many endogenous and exogenous compounds, including both toxic and therapeutic agents.

Original languageEnglish (US)
Pages (from-to)816-820
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume243
Issue number3
DOIs
StatePublished - Feb 24 1998

Bibliographical note

Funding Information:
This work was supported by PHS Grant R15 NS OD35364 and a Nebraska Department of Health, Cancer and Smoking Related Diseases grant.

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