Expression of intestinal transporter genes in beagle dogs

Abstract

This study was performed to produce a transcriptional database of the intestinal transporters of beagle dogs. Total RNA was isolated from the duodenum and the expression of various mRNAs was measured using GeneChip® oligonucleotide arrays. A total of 124 transporter genes were detected. Genes for fatty acid, peptide, amino acid and glucose and multidrug resistance/multidrug resistance-associated protein (MDR/MRP) transport were expressed at relatively higher levels than the other transporter types. The dogs exhibited abundant mRNA expression of the fatty acid transporters (fatty acid binding proteins, FABPs) FABP1 and FABP2, the ATP-binding cassettes (ABCs) ABCB1A and ABCC2, the amino acid/peptide transporters SLC3A1 and SLC15A1, the glucose transporters SLC5A1, SLC2A2 and SLC2A5, the organic anion transporter SLC22A9 and the phosphate transporters SLC20A1 and SLC37A4. In mice, a similar profile was observed with high expression of the glucose transporters SLC5A1 and SLC2As, the fatty acid transporters FABP1 and FABP2, the MDR/MRP transporters ABCB1A and ABCC2 and the phosphate transporter SLC37A4. However, the overall data reveal diverse transcriptomic profiles of the intestinal transporters of dogs and mice. Therefore, the current database may be useful for comparing the intestinal transport systems of dogs with those of mice to better evaluate xenobiotics.

Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor, EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development

“…There is limited information available on specific transporters in cats besides a lack of ATP-binding cassette G2 transporters [ 5 , 34 , 35 ]; however, based on the stability in vitro in liver microsomes and S9 fractions, a unique species-specific interaction with a transporter may explain the low oral bioavailability in cats and increased exposure in dogs. Due to the use of dogs as the preferred tox species in the development of human drugs, much more is known about the expression of dog transporters; but even in dogs, little is known about the functional role these changes play in the absorption or elimination of xenobiotics [ 41 , 42 ]. It is possible that other factors influenced PK.…”