Elsevier

Life Sciences

Volume 51, Issue 18, 1992, Pages 1427-1437
Life Sciences

P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells

https://doi.org/10.1016/0024-3205(92)90537-YGet rights and content

Abstract

The expression of a functional P-glycoprotein (P-gp) which pumps drugs out of brain capillary endothelial cells (BCEC) into blood was studied by evaluating the steady-state uptake and efflux of vincristine (VCR) by primary cultured bovine BCEC. The steady-state uptake of VCR was increased in the presence of metabolic inhibitors, and an anti-P-gp monoclonal antibody, MRK16, as well as verapamil and steroid hormones which are known to reverse multidrug resistance in tumor cells. Furthermore, efflux of VCR from BCEC was inhibited by verapamil. By immunohistochemistry, P-gp was localized at the luminal side of the capillary endothelial cells in both gray matter of bovine brain and primary cultured BCEC. These data suggest that P-gp functions as a drug efflux pump at the luminal side of BCEC and regulates the transfer of certain lipophilic drugs from the blood into the brain.

References (28)

  • R.L. Juliano et al.

    Biochim. Biophys. Acta

    (1976)
  • M.M. Gottesman et al.

    J. Biol. Chem.

    (1988)
  • F.L. Guillot et al.

    Microvas. Res.

    (1990)
  • O.H. Lowry et al.

    J. Biol. Chem.

    (1951)
  • C.-P.H. Yang et al.

    J. Biol. Chem.

    (1990)
  • M. Naito et al.

    J. Biol. Chem.

    (1988)
  • E.M. Cornford

    Mol. Physiol.

    (1985)
  • W.M. Pardridge

    Physiol. Rev.

    (1983)
  • V.A. Levin

    J. Med. Chem.

    (1980)
  • N.H. Greig et al.

    Cancer Chemother. Pharmacol.

    (1990)
  • J.A. Endicott et al.

    Annu. Rev. Biochem.

    (1989)
  • T. Skovsgaard

    Cancer Res.

    (1978)
  • M. Inaba et al.

    Cancer Res.

    (1979)
  • C. Cordon-Cardo et al.

    J. Histochem. Cytochem.

    (1990)
  • Cited by (296)

    • Drug Delivery to the Brain: Pharmacokinetic Concepts

      2017, Nanotechnology Methods for Neurological Diseases and Brain Tumors: Drug Delivery across the Blood-Brain Barrier
    • Quantitative Determination of Luminal and Abluminal Membrane Distributions of Transporters in Porcine Brain Capillaries by Plasma Membrane Fractionation and Quantitative Targeted Proteomics

      2015, Journal of Pharmaceutical Sciences
      Citation Excerpt :

      Among SLC transporters, GLUT1, monocarboxylate transporter 1 (MCT1/SLC16A1), fatty acid transport protein 1 (FATP1/SLC27A1), ATA2, and OATP3A1 were quantified, and GLUT1 exhibited the greatest expression among them in all fractions (Table 2). The luminal (fL) and abluminal distribution ratios (fA) were calculated to investigate the membrane localization of transporters in porcine brain capillary endothelial cells, employing MDR1 and ATA2 as luminal and abluminal marker proteins, respectively.3,4,7 Among all quantified molecules, MDR1 showed the greatest fraction distribution ratio (0.388) in fraction #1, and ATA2 showed the greatest ratio (0.517) in fraction #4, without correction for cross-contamination.

    View all citing articles on Scopus
    View full text