Genetic deficiency of carnitine/organic cation transporter 2 (slc22a5) is associated with altered tissue distribution of its substrate pyrilamine in mice

Biopharmaceutics and Drug Disposition

Volumn 30, Issue 9, 2009, Pages 495-507

  Katoa, Sayaka ^a   Katoa, Yukio ^a   Nakamuraa, Tadakatsu ^a   Sugiuraa, Tomoko ^a   Kuboa, Yoshiyuki ^a   Deguchib, Yoshiharu ^b   Tsujia, Akira ^a  

^a KANAZAWA UNIVERSITY   (Japan)

^b TEIKYO UNIVERSITY   (Japan)

Author keywords

Heart; Kidney; Octn2; Pharmacokinetics; Pyrilamine

Indexed keywords

ASTEMIZOLE; CARNITINE; CYPROHEPTADINE; EBASTINE; HISTAMINE H1 RECEPTOR ANTAGONIST; MEPYRAMINE; ORGANIC CATION TRANSPORTER 2; PRESTIN; TERFENADINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; DRUG ACCUMULATION; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG TRANSPORT; DRUG UPTAKE; GENE; GENETIC DISORDER; HEART; KIDNEY PARENCHYMA; MALE; MOUSE; NONHUMAN; OCTN2 GENE; SLC22A5 GENE; STEATOSIS; TEMPERATURE; TISSUE DISTRIBUTION; TISSUE SLICE; URINARY EXCRETION; WILD TYPE;

ANIMALS; DOWN-REGULATION; HISTAMINE H1 ANTAGONISTS; INJECTIONS, INTRAVENOUS; MALE; MICE; MICE, MUTANT STRAINS; ORGANIC CATION TRANSPORT PROTEINS; PYRILAMINE; TEMPERATURE; TISSUE DISTRIBUTION;

EID: 73349129723     PISSN: 01422782     EISSN: 1099081X     Source Type: Journal    
DOI: 10.1002/bdd.681     Document Type: Article

References (35)

1. Wu X, Prasad PD, Leibach FH, Ganapathy V. cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun 1998; 246: 589-595.
2. Tamai I, Ohashi R, Nezu J, et al. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 1998; 273: 20378-20382.
3. Nezu J, Tamai I, Oku A, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 1999; 21: 91-94.
4. Hashimoto N, Suzuki F, Tamai I, et al. Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS mice as a model of human carnitine transporter deficiency. Biochem Pharmacol 1998; 55: 1729-1732.
5. Lu K, Nishimori H, Nakamura Y, Shima K, Kuwajima M. A missense mutation of mouse OCTN2, a sodium-dependent carnitine cotransporter, in the juvenile visceral steatosis mouse. Biochem Biophys Res Commun 1998; 252: 590-594.
6. Yokogawa K, Miya K, Tamai I, et al. Characteristics of L-carnitine transport in cultured human hepatoma HLF cells. J Pharm Pharmacol 1999; 51: 935-940.
7. Yokogawa K, Higashi Y, Tamai I, et al. Decreased tissue distribution of L-carnitine in juvenile visceral steatosis mice. J Pharmacol Exp Ther 1999; 289: 224-230.
8. Yokogawa K, Yonekawa M, Tamai I, et al. Loss of wild-type carrier-mediated L-carnitine transport activity in hepatocytes of juvenile visceral steatosis mice. Hepatology 1999; 30: 997-1001.
9. Kato Y, Sugiura M, Sugiura T, et al. Organic cation/carnitine transporter OCTN2 (Slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse. Mol Pharmacol 2006; 70: 829-837.
10. Tamai I, Nakanishi T, Kobayashi D, et al. Involvement of OCTN1 (SLC22A4) in pH-dependent transport of organic cations. Mol Pharm 2003; 1: 57-66.
11. Ohashi R, Tamai I, Nezu Ji J, et al. Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol 2001; 59: 358-366.
12. Ohashi R, Tamai I, Yabuuchi H, et al. Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther 1999; 291: 778-784.
13. Wu X, Huang W, Prasad PD, et al. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther 1999; 290: 1482-1492.
14. Ganapathy ME, Huang W, Rajan DP, et al. Bactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem 2000; 275: 1699-1707.
15. Grigat S, Fork C, Bach M, et al. The carnitine transporter SLC22A5 is not a general drug transporter, but it efficiently translocates mildronate. Drug Metab Dispos 2009; 37: 330-337.
16. Kano T, Kato Y, Ito K, Ogihara T, Kubo Y, Tsuji A. Carnitine/organic cation transporter OCTN2 (Slc22a5) is responsible for renal secretion of cephaloridine in mice. Drug Metab Dispos 2009; 37: 1009-1016.
17. Tsuji A, Terasaki T, Takabatake Y, et al. P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Life Sci 1992; 51: 1427-1437.
18. Schinkel AH, Smit JJ, van Tellingen O, et al. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994; 20: 491-502.
19. 1-antagonist ebastine and its metabolite carebastine. J Drug Target 2000; 8: 383-393.
20. 1-antagonists. Drug Metab Dispos 2003; 31: 312-318.
21. Mitcheson JS, Chen J, Lin M, Culberson C, Sanguinetti MC. A structural basis for drug-induced long QT syndrome. Proc Natl Acad Sci USA 2000; 97: 12329-12333.
22. García-Ferreiro RE, Kerschensteiner D, Major F, Monje F, Stühmer W, Pardo LA. Mechanism of block of hEag1 K+channels by imipramine and astemizole. J Gen Physiol 2004; 124: 301-317.
23. Iwata D, Kato Y, Wakayama T, et al. Involvement of carnitine/organic cation transporter OCTN2 (SLC22A5) in distribution of its substrate carnitine to the heart. Drug Metab Pharmacokinet 2008; 23: 207-215.
24. Koizumi T, Nikaido H, Hayakawa J, Nonomura A, Yoneda T. Infantile disease with microvesicular fatty infiltration of viscera spontaneously occurring in the C3H-H-2(0) strain of mouse with similarities to Reye's syndrome. Lab Anim 1988; 22: 83-87.
25. Yamaoka K, Tanigawara Y, Nakagawa T, Uno T. A pharmacokinetic analysis program (MULTI) for microcomputer. J Pharmacobiodyn 1981; 4: 879-885.
26. Kelly DW, Slikker Jr W. The metabolism and elimination of pyrilamine maleate in the rat. Drug Metab Dispos 1987; 15: 460-465.
27. Tamai I, Ohashi R, Nezu JI, et al. Molecular and functional characterization of organic cation/ carnitine transporter family in mice. J Biol Chem 2000; 275: 40064-40072.
28. Grube M, Meyer zu Schwabedissen HE, Präger D, et al. Uptake of cardiovascular drugs into the human heart: expression, regulation, and function of the carnitine transporter OCTN2 (SLC22A5). Circulation 2006; 113: 1114-1122.
29. Zwart R, Verhaagh S, BuitelaarM, Popp-Snijders C, Barlow DP. Impaired activity of the extraneuronal monoamine transporter system known as uptake-2 in Orct3/Slc22a3-deficient mice. Mol Cell Biol 2001; 21: 4188-4196.
30. van Asperen J, Schinkel AH, Beijnen JH, Nooijen WJ, Borst P, van Tellingen O. Altered pharmacokinetics of vinblastine in Mdr1a P-glycoprotein-deficient mice. J Nat Cancer Inst 1996; 88: 994-999.
31. Sasabe H, Kato Y, Suzuki T, Itose M, Miyamoto G, Sugiyama Y. Differential involvement of multidrug resistance-associated protein 1 and P-glycoprotein in tissue distribution and excretion of grepafloxacin in mice. J Pharmacol Exp Ther 2004; 310: 648-655.
32. 1-antagonist at the blood-brain barrier: transport mechanism of mepyramine using the carotid injection technique. Biol Pharm Bull 1994; 17: 676-679.
33. 1-antagonists and lipophilic basic drugs. Pharm Res 1994; 11: 1516-1518.
34. Okura T, Hattori A, Takano Y, et al. Involvement of the pyrilamine transporter, a putative organic cation transporter, in blood-brain barrier transport of oxycodone. Drug Metab Dispos 2008; 36: 2005-2013.
35. 1-antagonist at the blood-brain barrier: mepyramine uptake into bovine brain capillary endothelial cells in primary monolayer cultures. Pharm Res 1994; 11: 975-978.