Functional expression of rat ABCG2 on the luminal side of brain capillaries and its enhancement by astrocyte-derived soluble factor(s)

J Neurochem. 2004 Aug;90(3):526-36. doi: 10.1111/j.1471-4159.2004.02537.x.


The purpose of the present study was to clarify the expression, transport properties and regulation of ATP-binding cassette G2 (ABCG2) transporter at the rat blood-brain barrier (BBB). The rat homologue of ABCG2 (rABCG2) was cloned from rat brain capillary fraction. In rABCG2-transfected HEK293 cells, rABCG2 was detected as a glycoprotein complex bridged by disulfide bonds, possibly a homodimer. The protein transported mitoxantrone and BODIPY-prazosin. In rat brain capillary fraction, rABCG2 protein was also detected as a glycosylated and disulfide-linked complex. Immunohistochemical analysis revealed that rABCG2 was localized mainly on the luminal side of rat brain capillaries, suggesting that rABCG2 is involved in brain-to-blood efflux transport. For the regulation study, conditionally immortalized rat brain capillary endothelial (TR-BBB13), astrocyte (TR-AST4) and pericyte (TR-PCT1) cell lines were used as an in vitro BBB model. Following treatment of TR-BBB13 cells with conditioned medium of TR-AST4 cells, the Ko143 (an ABCG2-specific inhibitor)-sensitive transport activity and rABCG2 mRNA level were significantly increased, whereas conditioned medium of TR-PCT1 cells had no effect. These results suggest that rat brain capillaries express functional rABCG2 protein and that the transport activity of the protein is up-regulated by astrocyte-derived soluble factor(s) concomitantly with the induction of rABCG2 mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Amino Acid Sequence
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Base Sequence
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / physiology
  • Brain / blood supply*
  • Brain / metabolism
  • Capillaries / cytology
  • Capillaries / metabolism*
  • Cell Membrane / metabolism
  • Cell Polarity
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Male
  • Mitoxantrone / metabolism
  • Molecular Sequence Data
  • Pericytes / cytology
  • Pericytes / metabolism
  • Prazosin / analogs & derivatives
  • Prazosin / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transfection


  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Abcg2 protein, rat
  • Culture Media, Conditioned
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Mitoxantrone
  • Prazosin

Associated data

  • GENBANK/AB105817