Abstract
Our work contributes to the understanding of the mechanisms of drug resistance in epilepsis. This study aimed to investigate i) the levels of expression of P-glycoprotein (P-gp), and multidrug resistance-associated proteins (MRP)1 and 2, ii) the activation of the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), and iii) the relationship between increased P-gp and MRPs expression and PXR and CAR activation, in immortalized rat brain microvascular endothelial cell lines, GPNT and RBE4, following treatment with the antiepileptic drugs (AEDs), topiramate, phenobarbital, carbamazepine, tiagabine, levetiracetam, and phenytoin, using Western blotting and immunocytochemistry methods. Carbamazepine, phenobarbital and phenytoin induced the highest levels of P-gp and MPRs expression that was associated with increased activation of PXR and CAR receptors as compared to levetiracetam, tiagabine and topiramate. We conclude that P-gp and MRPs are differently overexpressed in GPNT and RBE4 by various AEDs and both PXR and CAR are involved in the drug-resistant epilepsy induced by carbamazepine, phenobarbital and phenytoin.
Keywords: Epilepsy, drug resistance, cerebral microvascular endothelial cells, P-glycoprotein, multidrug resistanceassociated proteins, pregnane X receptor, androstane receptor, cytochrome P450
Current Neurovascular Research
Title: Induction of Nuclear Receptors and Drug Resistance in the Brain Microvascular Endothelial Cells Treated with Antiepileptic Drugs
Volume: 5 Issue: 2
Author(s): Laura Lombardo, Rosalia Pellitteri, Michael Balazy and Venera Cardile
Affiliation:
Keywords: Epilepsy, drug resistance, cerebral microvascular endothelial cells, P-glycoprotein, multidrug resistanceassociated proteins, pregnane X receptor, androstane receptor, cytochrome P450
Abstract: Our work contributes to the understanding of the mechanisms of drug resistance in epilepsis. This study aimed to investigate i) the levels of expression of P-glycoprotein (P-gp), and multidrug resistance-associated proteins (MRP)1 and 2, ii) the activation of the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), and iii) the relationship between increased P-gp and MRPs expression and PXR and CAR activation, in immortalized rat brain microvascular endothelial cell lines, GPNT and RBE4, following treatment with the antiepileptic drugs (AEDs), topiramate, phenobarbital, carbamazepine, tiagabine, levetiracetam, and phenytoin, using Western blotting and immunocytochemistry methods. Carbamazepine, phenobarbital and phenytoin induced the highest levels of P-gp and MPRs expression that was associated with increased activation of PXR and CAR receptors as compared to levetiracetam, tiagabine and topiramate. We conclude that P-gp and MRPs are differently overexpressed in GPNT and RBE4 by various AEDs and both PXR and CAR are involved in the drug-resistant epilepsy induced by carbamazepine, phenobarbital and phenytoin.
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Cite this article as:
Lombardo Laura, Pellitteri Rosalia, Balazy Michael and Cardile Venera, Induction of Nuclear Receptors and Drug Resistance in the Brain Microvascular Endothelial Cells Treated with Antiepileptic Drugs, Current Neurovascular Research 2008; 5 (2) . https://dx.doi.org/10.2174/156720208784310196
DOI https://dx.doi.org/10.2174/156720208784310196 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
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