Modulation of p-glycoprotein transport function at the blood-brain barrier

Björn Bauer, Anika M.S. Hartz, Gert Fricker, David S. Miller

Research output: Contribution to journalShort surveypeer-review

122 Scopus citations


The central nervous system (CNS) effects of many therapeutic drugs are blunted because of restricted entry into the brain. The basis for this poor permeability is the brain capillary endothelium, which comprises the blood-brain barrier. This tissue exhibits very low paracellular (tight-junctional) permeability and expresses potent, multispecific, drug export pumps. Together, these combine to limit use of pharmacotherapy to treat CNS disorders such as brain cancer and bacterial or viral infections. Of all the xenobiotic efflux pumps highly expressed in brain capillary endothelial cells, p-glycoprotein handles the largest fraction of commonly prescribed drugs and thus is an obvious target for manipulation. Here we review recent studies focused on understanding the mechanisms by which p-glycoprotein activity in the blood-brain barrier can be modulated. These include (i) direct inhibition by specific competitors, (ii) functional modulation, and (iii) transcriptional modulation. Each has the potential to specifically reduce p-glycoprotein function and thus selectively increase brain permeability of p-glycoprotein substrates.

Original languageEnglish
Pages (from-to)118-127
Number of pages10
JournalExperimental Biology and Medicine
Issue number2
StatePublished - Feb 2005


  • ATP-binding cassette
  • Central nervous system pharmacotherapy
  • Endothelin
  • Nuclear receptors
  • Regulation

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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