Animal species differences in the pyridoxine transport function of SLC19A3: Absence of Slc19a3-mediated pyridoxine uptake in the rat small intestine

The thiamine transporters, SLC19A2 and SLC19A3, have recently been shown to transport pyridoxine in addition to thiamine, the originally identified substrate, in our study on human orthologs. Based on these results, we characterized the rat and mouse orthologs for pyridoxine transport function. Through the assessment of pyridoxine uptake in human embryonic kidney 293 cells transiently expressing the SLC19A2/3 orthologs, we found that both rat and mouse Slc19a2 can transport pyridoxine, but rat or mouse Slc19a3 cannot. However, all SLC19A2/3 orthologs were capable of thiamine transport. We subsequently demonstrated in the rat small intestine that a carrier-mediated mechanism exists for thiamine uptake, but not for pyridoxine uptake. This is supported by the finding that rat Slc19a3, for which the human ortholog operates for the intestinal uptake of both pyridoxine and thiamine, lacks the pyridoxine transport function. Thus, SLC19A3s from different animal species exhibit differences in pyridoxine transport. Rats and mice, in which Slc19a3 lacks this function, are not suitable model animals for studies involving pyridoxine disposition and related issues.