IN VITRO P-GLYCOPROTEIN INHIBITION
ASSAY ON N2a MURINE CELL LINE
ALINA CRENGUŢA NICOLAE1, NICULINA MITREA1, ANDREEA
LETIŢIA ARSENE*1, MARIA ZINAIDA CONSTANTINESCU1,
VLAD VUȚĂ2, CRISTINA MANUELA DRĂGOI1
1Department of Biochemistry, Faculty of Pharmacy, University of
Medicine and Pharmacy ”Carol Davila”, 6, Traian Vuia Str, sector 2,
Bucharest, Romania
2Virology Department, Institute for Diagnosis and Animal Health, 63 Dr.
Staicovici Str, sector 5, Bucharest, Romania
*corresponding author: andreeanitulescu@hotmail.com
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Abstract:

P-glycoprotein (Pgp), also called MDR1, the product of the multidrug resistance (MDR) gene, is an ATP-dependent efflux transporter that affects the absorption, distribution, and excretion of a great number of clinically important drugs. Modulation of P-glycoprotein (Pgp) through inhibition or induction can lead to interactions at the level of the central nervous system (CNS) or intestinal, renal, or biliary efflux, having consequences upon treatment optimization. In order to reveal the Pgp effect of some CNS important drugs, we investigated five structurally diverse active substances: valproic acid (V), fluoxetine hydrochloride (F), risperidone (R), thioridazine hydrochloride (T) and lithium carbonate (L) for their ability to inhibit Pgp, compared to quinidine (Q), a classic Pgp inhibitor. Pgp inhibition was studied in temporal dynamics (different cell-drug contact times), by a fluorimetric assay using calcein-acetoxymethylester as fluorophore, on the murine neuroblastoma cell line N2a. Modulation of P-glycoprotein was accomplished using a physiological concentration of glutathione (GSH), on the cell line treated with the studied drugs.

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