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

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.

• Authors: Annett Spudich, Ertugrul Kilic, Hongyi Xing, Ulkan Kilic, Katharina M Rentsch, Heidi Wunderli-Allenspach, Claudio L Bassetti, Dirk M Hermann
• Journal: Nature neuroscience (Nat Neurosci) Vol. 9 Issue 4 Pg. 487-8 (Apr 2006) ISSN: 1097-6256 [Print] United States
• PMID: 16565717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors, genetics, metabolism)
• Animals
• Blood-Brain Barrier (physiology)
• Brain (anatomy & histology, physiology)
• Brain Ischemia (drug therapy, metabolism, pathology)
• Capillaries (cytology, 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)