The use of microdialysis techniques in mice to study P-gp function at the blood-brain barrier

István Sziráki, Franciska Erdo, Péter Trampus, Mirabella Sike, Petra Magdolna Molnár, Zsuzsanna Rajnai, Judit Molnár, I. Wilhelm, Csilla Fazakas, Emese Kis, I. Krizbai, Péter Krajcsi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)430-440
Number of pages11
JournalJournal of Biomolecular Screening
Volume18
Issue number4
DOIs
Publication statusPublished - Apr 2013

Fingerprint

Quinidine
Microdialysis
P-Glycoprotein
Blood-Brain Barrier
Brain
Drug interactions
Assays
Drug Interactions
Transcytosis
Dialysis Solutions
Endothelial cells
Testing
Drug Combinations
Substrates
Pharmaceutical Preparations
Transgenic Mice
Rats
Monolayers
Animals
Blood

Keywords

  • DDIs at BBB in mice
  • dual-probe microdialysis
  • pMBMEC monolayer assay
  • PSC-833
  • quinidine

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology

Cite this

Sziráki, I., Erdo, F., Trampus, P., Sike, M., Molnár, P. M., Rajnai, Z., ... Krajcsi, P. (2013). The use of microdialysis techniques in mice to study P-gp function at the blood-brain barrier. Journal of Biomolecular Screening, 18(4), 430-440. https://doi.org/10.1177/1087057112468156

The use of microdialysis techniques in mice to study P-gp function at the blood-brain barrier. / Sziráki, István; Erdo, Franciska; Trampus, Péter; Sike, Mirabella; Molnár, Petra Magdolna; Rajnai, Zsuzsanna; Molnár, Judit; Wilhelm, I.; Fazakas, Csilla; Kis, Emese; Krizbai, I.; Krajcsi, Péter.

In: Journal of Biomolecular Screening, Vol. 18, No. 4, 04.2013, p. 430-440.

Research output: Contribution to journalArticle

Sziráki, I, Erdo, F, Trampus, P, Sike, M, Molnár, PM, Rajnai, Z, Molnár, J, Wilhelm, I, Fazakas, C, Kis, E, Krizbai, I & Krajcsi, P 2013, 'The use of microdialysis techniques in mice to study P-gp function at the blood-brain barrier', Journal of Biomolecular Screening, vol. 18, no. 4, pp. 430-440. https://doi.org/10.1177/1087057112468156
Sziráki, István ; Erdo, Franciska ; Trampus, Péter ; Sike, Mirabella ; Molnár, Petra Magdolna ; Rajnai, Zsuzsanna ; Molnár, Judit ; Wilhelm, I. ; Fazakas, Csilla ; Kis, Emese ; Krizbai, I. ; Krajcsi, Péter. / The use of microdialysis techniques in mice to study P-gp function at the blood-brain barrier. In: Journal of Biomolecular Screening. 2013 ; Vol. 18, No. 4. pp. 430-440.
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