scholarly journals The aryl hydrocarbon receptor (AhR) upregulates P‐glycoprotein (P‐gp) at the blood‐brain barrier (BBB)

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
David S Miller ◽  
Xueqian Wang
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Glycoprotein P ◽  
Aryl Hydrocarbon ◽  
P Glycoprotein ◽  
Blood Brain

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

2011 ◽  
Vol 31 (6) ◽  
pp. 1371-1375 ◽  
Author(s):  
Xueqian Wang ◽  
Brian T Hawkins ◽  
David S Miller
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Transport Activity ◽  
Aryl Hydrocarbon ◽  
Kinase C ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Glycoprotein Transport ◽  
The Brain

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.

Tariquidar (TAR, XR-9576) selectively inhibits P-glycoprotein (P-gp) in t-lymphocytes compared to that in the blood-brain barrier (BBB)

2005 ◽  
Vol 77 (2) ◽  
pp. P39-P39 ◽  
Author(s):  
M MUSZKAT ◽  
D KURNIK ◽  
G SOFOWORA ◽  
J DONAHUE ◽  
G WILKINSON ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Blood Brain

scholarly journals THE ONTOGENY OF P-GLYCOPROTEIN IN THE DEVELOPING HUMAN BLOOD BRAIN BARRIER: IMPLICATION FOR OPIOID TOXICITY IN NEONATES

2015 ◽  
Vol 101 (1) ◽  
pp. e1.1-e1
Author(s):  
Gideon Koren ◽  
Jessica Lam ◽  
Lauren Kelly ◽  
Stephanie Baella ◽  
David Chitayat ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Systemic Circulation ◽  
Brain Barrier ◽  
Glycoprotein P ◽  
Postnatal Maturation ◽  
Luminal Membrane ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Life Threatening ◽  
The Brain

Neonates have been shown to have a heightened sensitivity to the central depressive effects of opioids compared to older infants and adults. The limited development of P-glycoprotein (P-gp), located on the luminal membrane of the brain endothelial cells, may limit the ability of the neonate to efflux morphine from the brain back to the systemic circulation. Presently, little is known about blood brain barrier P-gp expression during human development. The objective of the study was to determine the ontogeny of P-gp in the human BBB. Postmortem cortex samples from gestational age (GA) 20–26 weeks, GA 36–40 weeks, postnatal age (PNA) 0–3 months, PNA 3–6 months, and adults were immunostained for P-gp. Analysis was carried out by spinning disc confocal microscopy. The intensity of P-gp staining in adults was significantly higher compared to at GA 20–26 weeks (p=0.0002), GA 36–40 weeks (p=0.0002), and PNA 0–3 months (p=0.0044). P-gp intensity at GA 20–26 weeks (p=0.0011), GA 36–40 weeks (p=0.0013), and PNA 0–3 months (p=0.0173) was significantly lower compared to at PNA 3–6 months. P-gp expression in the BBB is limited at birth, increases with postnatal maturation, and reaches adult levels at approximately 3–6 months of age. Given the immaturity of BBB P-gp after birth, morphine may concentrate in the brain. This provides mechanistic support to life threatening opioid toxicity seen with maternal codeine use during breastfeeding.

The influence of mass of [11C]-laniquidar and [11C]-N-desmethyl-loperamide on P-glycoprotein blockage at the blood–brain barrier

2012 ◽  
Vol 39 (1) ◽  
pp. 121-125 ◽  
Author(s):  
Lieselotte Moerman ◽  
Caroline Dumolyn ◽  
Paul Boon ◽  
Filip De Vos
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain

The Strongest Expression of P-Glycoprotein is in the Blood-Brain Barrier

1996 ◽  
pp. 171-174 ◽  
Author(s):  
Edith Beaulieu ◽  
Michel Demeule ◽  
Diana A. Averill-Bates ◽  
Richard Béliveau
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain
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