Sequencing and tissue distribution of the canine MRP2 gene compared with MRP1 and MDR1

Citation
S. Conrad et al., Sequencing and tissue distribution of the canine MRP2 gene compared with MRP1 and MDR1, TOXICOLOGY, 156(2-3), 2001, pp. 81-91
Citations number
37
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGY
ISSN journal
0300483X → ACNP
Volume
156
Issue
2-3
Year of publication
2001
Pages
81 - 91
Database
ISI
SICI code
0300-483X(20010102)156:2-3<81:SATDOT>2.0.ZU;2-7
Abstract
The effects of xenobiotic drugs and toxic compounds depend largely on their kinetic properties, which can be influenced by transmembrane drug transpor ters like MDR1/P-glycoprotein and the drug-conjugate transporters multidrug resistance protein (MRP) 1 and 2. As the dog is a preferential species use d in the pharmacological and toxicological evaluation of new drugs, we sequ enced the canine MRP2 cDNA and investigated its expression ill various cani ne tissues compared with the related transporters MRP1 and P-glycoprotein. The tissue distribution pattern of these ABC-transporters differs partially from the distribution described in humans. So we found relatively high ren al and low hepatic canine MRP2 expression levels, relatively high hepatic c anine MRP1 expression levels, and quite high levels of MRP1 and P-glycoprot ein in the dog brain. The knowledge of the tissue distribution pattern of t hese transporters will aid to interpret pharmacokinetic and toxicokinetic d ata gained from dog studies and to extrapolate them to humans. (C) 2001 Els evier Science ireland Ltd. All rights reserved.