Abstract
Recent progress in the molecular identification of transporters has led to advances in unveiling animal species differences in the carrier-mediated disposition of nutrients and xenobiotics in the body. Notably, we now need to be aware that transporters may exhibit animal species differences in the transport function in a substrate-dependent manner, as found for SLC19A3/THTR2 and SLC22A2/OCT2 in our recent molecular and functional analyses comparing the human ortholog functional for a certain substrate with a nonfunctional one in some other animal. In SLC19A3, known as the intestinal thiamine uptake transporter with no animal species differences in that function, it was found that seven particular amino acid residues are specifically involved in the pyridoxine transport function newly found in human SLC19A3 and they are mostly conserved in several orthologs that can transport pyridoxine but not in those that cannot, such as rat and mouse orthologs. In SLC22A2, known as the basolaterally localized renal tubular organic cation transporter with no animal species differences in its transport function for major substrates, it was found that eight particular amino acid residues are specifically involved in the atenolol transport function found newly and only in human SLC22A2 and they are mostly unconserved in several orthologs which cannot transport atenolol. Such knowledge should help guide the utilization of experimental animals in studies on solute disposition which involves carrier-mediated mechanisms. Efforts should be needed to further accumulate relevant knowledge.
