ABC transporter function and regulation at the blood-spinal cord barrier

J Cereb Blood Flow Metab. 2012 Aug;32(8):1559-66. doi: 10.1038/jcbfm.2012.47. Epub 2012 Apr 4.

Abstract

We present here an initial characterization of ATP binding cassette (ABC) transporter function and regulation at the blood-spinal cord barrier. We isolated capillaries from rat spinal cords and studied transport function using a confocal microscopy-based assay and protein expression using western blots. These capillaries exhibited transport function and protein expression of P-glycoprotein (Abcb1), multidrug resistance protein 2 (Mrp2, Abcc2), and breast cancer-related protein (Bcrp, Abcg2). Exposing isolated capillaries to dioxin (activates aryl hydrocarbon receptor) increased transport mediated by all three transporters. Brain and spinal cord capillaries from dioxin-dosed rats exhibited increased P-glycoprotein-mediated transport and increased protein expression for all three ABC transporters. These findings indicate similar ABC transporter expression, function, and regulation at the blood-spinal cord and blood-brain barriers.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B* / genetics
  • ATP Binding Cassette Transporter, Subfamily B* / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters* / genetics
  • ATP-Binding Cassette Transporters* / metabolism
  • Animals
  • Biological Transport
  • Blood-Brain Barrier / metabolism*
  • Blotting, Western
  • Capillaries / metabolism
  • Cell Membrane / metabolism
  • Electrophoretic Mobility Shift Assay
  • Ligands
  • Male
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Polychlorinated Dibenzodioxins / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / blood supply*
  • Spinal Cord / metabolism*
  • Xenobiotics / pharmacokinetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Abcc2 protein, rat
  • Abcg2 protein, rat
  • Ligands
  • Polychlorinated Dibenzodioxins
  • Xenobiotics
  • multidrug resistance protein 3