Expression of intestinal transporter genes in beagle dogs

Cho,Soo‑Min; Park,Sung‑Won; Kim,Na‑Hyun; Park,Jin‑A; Yi,Hee; Cho,Hee‑Jung; Park,Ki‑Hwan; Hwang,Ingyun; Shin,Ho‑Chul

doi:10.3892/etm.2012.777

Expression of intestinal transporter genes in beagle dogs

Authors:
- Soo‑Min Cho
- Sung‑Won Park
- Na‑Hyun Kim
- Jin‑A Park
- Hee Yi
- Hee‑Jung Cho
- Ki‑Hwan Park
- Ingyun Hwang
- Ho‑Chul Shin
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Affiliations: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea, Toxicology and Chemistry Division, Animal Plant and Fisheries Quarantine and Inspection Agency, Anyang 430‑824, Republic of Korea, Department of Food Science __AMB__ Technology, Chung‑Ang University, Ansung 456‑756, Republic of Korea, Food Chemical Residues Division, Korea Food __AMB__ Drug Administration, Osong 363‑951, Republic of Korea
Published online on: October 30, 2012 https://doi.org/10.3892/etm.2012.777
Pages: 308-314

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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.

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1	Varma MV: Role of intestinal transporters and metabolism in the oral absorption of drug and prodrugs. Curr Drug Metab. 11:7152010. View Article : Google Scholar : PubMed/NCBI
2	Katsura T and Inui K: Intestinal absorption of drugs mediated by drug transporters: mechanisms and regulation. Drug Metab Pharmacokinet. 18:1–15. 2003. View Article : Google Scholar : PubMed/NCBI
3	Sugiura T, Kato Y and Tsuji A: Role of SLC xenobiotic transporters and their regulatory mechanisms PDZ proteins in drug delivery and disposition. J Control Release. 116:238–246. 2006. View Article : Google Scholar : PubMed/NCBI
4	Rankin KS, Starkey M, Lunec J, et al: Of dogs and men: comparative biology as a tool for the discovery of novel biomarkers and drug development targets in osteosarcoma. Pediatr Blood Cancer. 58:327–333. 2012. View Article : Google Scholar : PubMed/NCBI
5	Wang W, Jiang J, Ballard CE and Wang B: Prodrug approaches to the improved delivery of peptide drugs. Curr Pharm Des. 5:265–287. 1999.PubMed/NCBI
6	Shin HC, Kim HR, Cho HJ, et al: Comparative gene expression of intestinal metabolizing enzymes. Biopharm Drug Dispos. 30:411–421. 2009. View Article : Google Scholar : PubMed/NCBI
7	Fang H, Tong W, Perkins R, et al: Bioinformatics approaches for cross-species liver cancer analysis based on microarray gene expression profiling. BMC Bioinformatics. 6(Suppl 2): S62005. View Article : Google Scholar : PubMed/NCBI
8	Landowski CP, Sun D, Foster DR, et al: Gene expression in the human intestine and correlation with oral valacyclovir pharmacokinetic parameters. J Pharmacol Exp Ther. 306:778–786. 2003. View Article : Google Scholar : PubMed/NCBI
9	Takara K, Ohnishi N, Horibe S and Yokayama T: Expression profiles of drug-metabolizing enzyme CYP3A and drug efflux transporter multidrug resistance 1 subfamily mRNAS in small intestine. Drug Metab Dispos. 31:1235–1239. 2003. View Article : Google Scholar
10	Rushmore TH and Kong AN: Pharmacogenomics, regulation and signaling pathways of phase I and II drug metabolizing enzymes. Curr Drug Metab. 3:481–490. 2002. View Article : Google Scholar : PubMed/NCBI
11	Mizuno N, Niwa T, Yotsumoto Y and Sugiyama Y: Impact of drug transporter studies on drug discovery and development. Pharmacol Rev. 55:425–461. 2003. View Article : Google Scholar : PubMed/NCBI
12	Beaumont K: The importance of gut wall metabolism in determining drug bioavailability. Drug Bioavailability/Estimation of Solubility, Permeability and Absorption. van de Waterbeemd H, Lennernas H and Artursson P: Wiley-VCH; Weinheim: pp. 311–328. 2003
13	Tsuji A: Transporter-mediated drug interactions. Drug Metab Pharmacokinet. 17:253–274. 2002. View Article : Google Scholar
14	Mizuma T, Ohta K and Awazu S: The beta-anomeric and glucose preferences of glucose transport carrier for intestinal active absorption of monosaccharide conjugates. Biochim Biophys Acta. 1200:117–122. 1994. View Article : Google Scholar : PubMed/NCBI
15	Zhao FQ and Keating AF: Expression and regulation of glucose transporters in the bovine mammary gland. J Dairy Sci. 90(Suppl 1): E76–E86. 2007. View Article : Google Scholar : PubMed/NCBI
16	Stelmańskan E: The important role of GLUT2 in intestinal sugar transport and absorption. Postepy Biochem. 55:385–387. 2009.(In Polish).
17	Phay JE, Hussain HB and Moley JF: Cloning and expression analysis of a novel member of the facilitative glucose transporter family, SLC2A9 (GLUT9). Genomics. 66:217–220. 2000. View Article : Google Scholar : PubMed/NCBI
18	Tate BJ, Witort E, McKenzie IF and Hogarth PM: Expression of the high responder/non-responder human Fc gamma RII. Analysis by PCR and transfection into FcR-COS cells. Immunol Cell Biol. 70(Pt 2): 79–87. 1992. View Article : Google Scholar : PubMed/NCBI
19	Wells RG and Hediger MA: Cloning of a rat kidney cDNA that stimulates dibasic and neutral amino acid transport and has sequence similarity to glucosidases. Proc Natl Acad Sci USA. 89:5596–5600. 1992. View Article : Google Scholar : PubMed/NCBI
20	Seal CJ and Parker DS: Isolation and characterization of circulating low molecular weight peptides in steer, sheep and rat portal and peripheral blood. Comp Biochem Physiol B. 99:679–685. 1991.PubMed/NCBI
21	Lee VH, Chu C, Mahlin ED, et al: Biopharmaceutics of transmucosal peptide and protein drug administration: role of transport mechanisms with a focus on the involvement of PepT1. J Control Release. 62:129–140. 1999. View Article : Google Scholar : PubMed/NCBI
22	Kim HR, Park SW, Cho HJ, et al: Comparative gene expression profiles of intestinal transporters in mice, rats and humans. Pharmacol Res. 56:224–236. 2007. View Article : Google Scholar : PubMed/NCBI
23	Abumrad N, Harmon C and Ibrahimi A: Membrane transport of long-chain fatty acids: evidence for a facilitated process. J Lipid Res. 39:2309–2318. 1998.PubMed/NCBI
24	Thumser AE and Storch J: Liver and intestinal fatty acid-binding proteins obtain fatty acids from phospholipid membranes by different mechanisms. J Lipid Res. 41:647–656. 2000.PubMed/NCBI
25	Schaffer JE and Lodish HF: Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein. Cell. 79:427–436. 1994. View Article : Google Scholar : PubMed/NCBI
26	Traut TW: Physiological concentrations of purines and pyrimidines. Mol Cell Biochem. 140:1–22. 1994. View Article : Google Scholar : PubMed/NCBI
27	el Kouni MH: Trends in the design of nucleoside analogues as anti-HIV drugs. Curr Pharm Des. 8:581–593. 2002.PubMed/NCBI
28	Damaraju VL, Damaraju S, Young JD, et al: Nucleoside anti-cancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy. Oncogene. 22:7524–7536. 2003. View Article : Google Scholar : PubMed/NCBI
29	Sandusky GE, Mintze KS, Pratt SE and Dantzig AH: Expression of multidrug resistance-associated protein 2 (MRP2) in normal human tissues and carcinomas using tissue microarrays. Histopathology. 41:65–74. 2002. View Article : Google Scholar
30	Tang F and Borchardt RT: Characterization of the efflux transporter(s) responsible for restricting intestinal mucosa permeation of an acyloxyalkoxy-based cyclic prodrug of the opioid peptide DADLE. Pharm Res. 19:780–786. 2002. View Article : Google Scholar
31	Miyazaki H, Sekine T and Endou H: The multispecific organic anion transporter family: properties and pharmacological significance. Trends Pharmacol Sci. 25:654–662. 2004. View Article : Google Scholar : PubMed/NCBI
32	Bahn A, Hagos Y, Reuter S, et al: Identification of a new urate and high affinity nicotinate transporter, hOAT10 (SLC22A13). J Biol Chem. 283:16332–16341. 2008. View Article : Google Scholar : PubMed/NCBI