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.
Highlights
Intestinal drug transporters have great potential for drug absorption [1,2]
It is accepted that the process of drug absorption in the intestine is highly associated with the functional expression of intestinal transporters [5]
It is accepted that the process of drug absorption in the intestine is highly associated with the functional gene expression of intestinal transporters [8]
Summary
Intestinal drug transporters have great potential for drug absorption [1,2] They may serve as either drug targets or drug delivery systems. Various types of xenobiotic or drug transporters have been identified as being important as barriers against toxic compounds and influx pumps to take up nutrients into the body. Since these xenobiotic transporters generally have a wide range of recognition specificities and accept various types of compounds as substrates, the localization and functional expression of such transporters may be a critical factor in the disposition and subsequent biological activity of therapeutic agents. The current study was carried out to generate a gene expression database of transporters in the canine duodenum
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