Inhibition of multidrug resistance transporter-1 facilitates neuroprotective therapies after focal cerebral ischemia

Nat Neurosci. 2006 Apr;9(4):487-8. doi: 10.1038/nn1676. Epub 2006 Mar 26.

Abstract

The blood-brain barrier possesses active transporters carrying brain-permeable xenobiotics back into the blood against concentration gradients. We demonstrate that multidrug resistance transporter (Mdr)-1 is upregulated on capillary endothelium after focal cerebral ischemia; moreover, Mdr-1 deactivation by pharmacological inhibition or genetic knockout preferably enhances the accumulation and efficacy of two neuroprotectants known as Mdr-1 substrates in the ischemic brain. We predict that Mdr-1 inhibition may greatly facilitate neuroprotective therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Blood-Brain Barrier / physiology
  • Brain / anatomy & histology
  • Brain / physiology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Capillaries / cytology
  • Capillaries / metabolism
  • Cerebrovascular Circulation / physiology
  • Endothelium, Vascular / metabolism
  • Enzyme Inhibitors / metabolism
  • Immunosuppressive Agents / metabolism
  • Mice
  • Mice, Knockout
  • Neuroprotective Agents / therapeutic use*
  • Quinolines / metabolism*
  • Rifampin / metabolism
  • Tacrolimus / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Neuroprotective Agents
  • Quinolines
  • tariquidar
  • Rifampin
  • Tacrolimus