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

• Published in: Toxicology (Amsterdam) Vol. 156; no. 2-3; pp. 81 - 91
• Main Authors: Conrad, Silke, Viertelhaus, Anne, Orzechowski, Achim, Hoogstraate, Janet, Gjellan, Kirsti, Schrenk, Dieter, Kauffmann, Hans-Martin
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 02.01.2001; Amsterdam Elsevier Science
• Subjects: Ageing, cell death; Amino Acid Sequence; Animals; ATP Binding Cassette Transporter, Subfamily B - genetics; ATP Binding Cassette Transporter, Subfamily B - metabolism; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biological and medical sciences; Blotting, Western; Cell physiology; DNA, Complementary - analysis; Dogs; Drug Resistance, Multiple - genetics; Expression analysis; Fundamental and applied biological sciences. Psychology; Genes, MDR - genetics; Humans; Kidney - metabolism; Liver - metabolism; Male; mdr1 gene; MDR1/P-glycoprotein; Membrane Transport Proteins; Molecular and cellular biology; Molecular Sequence Data; MRP1 gene; MRP2 gene; Multidrug resistance protein 1; Multidrug resistance protein 2; Multidrug Resistance-Associated Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA - analysis; RNA, Messenger - analysis; Sequence Analysis, DNA; Species Specificity; Tissue Distribution; DMSO, dimethylsulphoxide; SDS-PAGE, sodium dodecyl sulphate polyacrylamide gel electrophoresis; Expression analysis; MDR1/P-glycoprotein; PMSF, phenylmethylsulphonylfluoride; ABC-transporter, ATP binding cassette transporter; MRP, multidrug resistance protein; Multidrug resistance protein 1; Multidrug resistance protein 2; DTT, dithiothreitol; MDR, multidrug resistance; Gene product; Liver; Lung; Central nervous system; Biodistribution; Kidney; Tissue; Membrane transport; Multiple resistance; Dog; Sequencing; Xenobiotic; Transmembrane protein; Fissipedia; Carnivora; Nucleotide sequence; Glycoprotein; Gut; Tissue specificity; Gene expression; In vitro; Vertebrata; Mammalia; Animal; ABC transporter
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(00)00354-1

The effects of xenobiotic drugs and toxic compounds depend largely on their kinetic properties, which can be influenced by transmembrane drug transporters like MDR1/P-glycoprotein and the drug-conjugate transporters multidrug resistance protein (MRP) 1 and 2. As the dog is a preferential species used in the pharmacological and toxicological evaluation of new drugs, we sequenced the canine MRP2 cDNA and investigated its expression in various canine 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 renal and low hepatic canine MRP2 expression levels, relatively high hepatic canine MRP1 expression levels, and quite high levels of MRP1 and P-glycoprotein in the dog brain. The knowledge of the tissue distribution pattern of these transporters will aid to interpret pharmacokinetic and toxicokinetic data gained from dog studies and to extrapolate them to humans.