• Article

Activating PKC-ß1 at the blood-brain barrier reverses induction of P-glycoprotein activity by dioxin and restores drug delivery to the CNS

Upregulation of blood–brain barrier (BBB) P-glycoprotein expression causes central nervous
system (CNS) pharmacoresistance. However, activation of BBB protein kinase C-b1 (PKC-b1) rapidly
reduces basal P-glycoprotein transport activity. We tested whether PKC-b1 activation would reverse
CNS drug resistance caused by dioxin acting through aryl hydrocarbon receptor. A selective PKC-b1
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-b1 may be an effective strategy to improve drug delivery to the brain, even in
drug-resistant individuals

Citation

Wang, X., Hawkins, B., & Miller, D. S. (2011). Activating PKC-ß1 at the blood-brain barrier reverses induction of P-glycoprotein activity by dioxin and restores drug delivery to the CNS. Journal of Cerebral Blood Flow and Metabolism, 31(6), 1371-1375. DOI: 10.1038/jcbfm.2011.44

DOI Links