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.