The Use of Microdialysis Techniques in Mice to Study P-gp Function at the Blood-Brain Barrier

An integrated assay system involving dual/triple-probe microdialysis techniques in rats was developed earlier for testing interactions with P-glycoprotein (P-gp) at the blood-brain barrier using quinidine/PSC-833 as a P-gp substrate/inhibitor combination. The aim of the present study was to expand o...

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Bibliographic Details
Main Authors: Sziraki I
Erdő Franciska
Trampus P
Sike M
Molnár Petra Magdolna
Narozsnikné Rajnai Zsuzsanna
Molnár Judit
Wilhelm Imola Mária
Fazakas Csilla
Kis Emese
Krizbai István Adorján
Krajcsi Péter
Format: Article
Published: 2013
Series:JOURNAL OF BIOMOLECULAR SCREENING 18 No. 4
Subjects:
Analitikai kémia
Biokémia
Farmakológia és gyógyszerészet
doi:10.1177/1087057112468156

mtmt:2169930
Online Access:https://publikacio.ppke.hu/2384
Description
Summary:An integrated assay system involving dual/triple-probe microdialysis techniques in rats was developed earlier for testing interactions with P-glycoprotein (P-gp) at the blood-brain barrier using quinidine/PSC-833 as a P-gp substrate/inhibitor combination. The aim of the present study was to expand our assay system to mice using microdialysis with simultaneous sampling of blood and brain and to compare the result with a primary mouse brain endothelial cell monolayer (pMBMEC) assay. Brain penetration of quinidine was dose dependent in both anesthetized and awake mice after intraperitoneal drug administration. PSC-833 pretreatment caused a 2.5- to 3.4-fold increase in quinidine levels of brain dialysate samples in anesthetized or awake animals, after single or repeated administration of PSC-833. In pMBMEC, a 2.0- to 2.5-fold efflux ratio was observed in the transcellular transport of quinidine. The P-gp-mediated vectorial transport of quinidine was eliminated by PSC-833. These results indicate that quinidine with PSC-833 is a good probe substrate-reference inhibitor combination for testing drug-drug interactions with P-gp in the in vivo and in vitro mouse systems. With increasing number of humanized transgenic mice, a test system with mouse microdialysis experimentation becomes more important to predict drug-drug interactions in humans.
Physical Description:430-440
ISSN:1087-0571

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