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

Sziráki, István and Erdő, Franciska and Trampus, Péter and Sike, Mirabella and Molnár, Petra Magdolna and Narozsnikné Rajnai, Zsuzsanna and Molnár, Judit and Wilhelm, Imola and Fazakas, Csilla and Kis, Emese and Krizbai, István Adorján and Krajcsi, Péter (2013) The Use of Microdialysis Techniques in Mice to Study P-gp Function at the Blood-Brain Barrier. JOURNAL OF BIOMOLECULAR SCREENING, 18 (4). pp. 430-440. ISSN 1087-0571

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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.

Item Type: Article
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Depositing User: MTMT SWORD
Date Deposited: 08 Apr 2014 07:26
Last Modified: 08 Apr 2014 07:26

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