Activating PKC-β1 at the blood-brain barrier reverses induction of P-glycoprotein activity by dioxin and restores drug delivery to the CNS.

Journal Article (letter;Journal Article)

Upregulation of blood-brain barrier (BBB) P-glycoprotein expression causes central nervous system (CNS) pharmacoresistance. However, activation of BBB protein kinase C-β1 (PKC-β1) rapidly reduces basal P-glycoprotein transport activity. We tested whether PKC-β1 activation would reverse CNS drug resistance caused by dioxin acting through aryl hydrocarbon receptor. A selective PKC-β1 agonist abolished the increase in P-glycoprotein activity induced by dioxin in isolated rat brain capillaries and reversed the effect of dioxin on brain uptake of verapamil in dioxin-dosed rats. Thus, targeting BBB PKC-β1 may be an effective strategy to improve drug delivery to the brain, even in drug-resistant individuals.

Full Text

Duke Authors

Cited Authors

  • Wang, X; Hawkins, BT; Miller, DS

Published Date

  • June 2011

Published In

Volume / Issue

  • 31 / 6

Start / End Page

  • 1371 - 1375

PubMed ID

  • 21487415

Pubmed Central ID

  • PMC3130326

Electronic International Standard Serial Number (EISSN)

  • 1559-7016

International Standard Serial Number (ISSN)

  • 0271-678X

Digital Object Identifier (DOI)

  • 10.1038/jcbfm.2011.44


  • eng