Conrad S, Viertelhaus A, Orzechowski A, Hoogstraate J, Gjellan K, Schrenk D, Kauffmann H M
Food Chemistry/Environmental Toxicology, University of Kaiserslautern, Erwin-Schroedinger-Strasse 52, D-67663 Kaiserslautern, Germany.
Toxicology. 2001 Jan 2;156(2-3):81-91. 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.
外源性药物和有毒化合物的作用很大程度上取决于它们的动力学特性，而这些特性会受到诸如MDR1/P-糖蛋白等跨膜药物转运蛋白以及药物共轭转运蛋白多药耐药相关蛋白（MRP）1和2的影响。由于犬类是新药药理和毒理学评估中常用的首选物种，我们对犬类MRP2 cDNA进行了测序，并与相关转运蛋白MRP1和P-糖蛋白相比，研究了其在犬类各种组织中的表达情况。这些ABC转运蛋白的组织分布模式与人类中描述的分布部分不同。因此，我们发现犬类MRP2在肾脏中的表达水平相对较高，而在肝脏中的表达水平较低，犬类MRP1在肝脏中的表达水平相对较高，并且在犬类大脑中MRP1和P-糖蛋白的水平相当高。了解这些转运蛋白的组织分布模式将有助于解释从犬类研究中获得的药代动力学和毒代动力学数据，并将其外推至人类。
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