Regulation of P-glycoprotein and other ABC drug transporters at the blood-brain barrier

Trends Pharmacol Sci. 2010 Jun;31(6):246-54. doi: 10.1016/ Epub 2010 Apr 24.


ATP-binding cassette (ABC) transporters are important selective elements of the blood-brain barrier. They line the luminal plasma membrane of the brain capillary endothelium, facing the vascular space, and both protect the central nervous system from entry of neurotoxicants and limit the access of therapeutic drugs to the brain parenchyma. Recent studies highlight the multiple signaling pathways through which the expression and activity of P-glycoprotein and other ABC transporters are modulated in response to xenobiotics, stress and disease. The results show that increased transporter expression occurs in response to signals that activate specific transcription factors, including pregnane-X receptor, constitutive androstane receptor, nuclear factor-kappaB and activator protein-1, and that reduced transporter activity occurs rapidly and reversibly in response to signaling through Src kinase, protein kinase C and estrogen receptors. A detailed understanding of such regulation can provide the basis for improved neuroprotection and enhanced therapeutic drug delivery to the brain.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / physiology
  • Central Nervous System Diseases / metabolism
  • Central Nervous System Diseases / physiopathology
  • Gene Expression Regulation / physiology*
  • Humans
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Stress, Physiological / physiology
  • Xenobiotics / adverse effects


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Xenobiotics