P-glycoprotein in blood-brain barrier endothelial cells: interaction and oligomerization with caveolins

J Neurochem. 2003 Nov;87(4):1010-23. doi: 10.1046/j.1471-4159.2003.02081.x.


P-glycoprotein (P-gp), an adenosine triphosphate (ATP)-binding cassette transporter which acts as a drug efflux pump, is highly expressed at the blood-brain barrier (BBB) where it plays an important role in brain protection. Recently, P-gp has been reported to be located in the caveolae of multidrug-resistant cells. In this study, we investigated the localization and the activity of P-gp in the caveolae of endothelial cells of the BBB. We used an in vitro model of the BBB which is formed by co-culture of bovine brain capillary endothelial cells (BBCEC) with astrocytes. Caveolar microdomains isolated from BBCEC are enriched in P-gp, cholesterol, caveolin-1, and caveolin-2. Moreover, P-gp interacts with caveolin-1 and caveolin-2; together, they form a high molecular mass complex. P-gp in isolated caveolae is able to bind its substrates, and the caveolae-disrupting agents filipin III and nystatin decrease P-gp transport activity. In addition, mutations in the caveolin-binding motif present in P-gp reduced the interaction of P-gp with caveolin-1 and increased the transport activity of P-gp. Thus, P-gp expressed at the BBB is mainly localized in caveolae and its activity may be modulated by interaction with caveolin-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Binding Sites / genetics
  • Binding Sites / physiology
  • Blood-Brain Barrier / metabolism*
  • Brain / blood supply
  • Capillaries / cytology
  • Cattle
  • Caveolae / chemistry
  • Caveolae / metabolism
  • Caveolin 1
  • Caveolin 2
  • Caveolins / metabolism*
  • Cells, Cultured
  • Coculture Techniques
  • Dogs
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Kidney / cytology
  • Kidney / metabolism
  • Macromolecular Substances
  • Models, Biological
  • Mutagenesis, Site-Directed
  • Protein Binding / physiology
  • Protein Transport / physiology
  • Rats


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cav1 protein, rat
  • Caveolin 1
  • Caveolin 2
  • Caveolins
  • Macromolecular Substances