Abstract
We succeeded in isolating the cDNA-encoding mouse organic solute carrier protein 1 (mOscp1) from a mouse testis cDNA library. mOscp1 consisted of 1137 base pairs that encoded a 379-amino acid protein, and the amino acid sequence was 85% identical to that of human OSCP1 (hOSCP1). Northern blot analysis revealed that the gene coding for mOscp1 is highly expressed in the testis, but not in other tissues. When expressed in Xenopus laevis oocytes, mOscp1 mediated the high-affinity transport of p-aminohippurate (PAH) (Km = 18.8 ± 4.1 μM) with Na+ independence. mOscp1 transported various kinds of structurally dissimilar drugs and chemicals such as probenecid, dehydroepiandrosterone sulfate, and glutarate with some differences in substrate specificity compared with hOSCP1. Cyclophosphamide inhibited the mOscp1-mediated PAH uptake. Immunohistochemical analysis revealed that the mOscp1 protein is localized in the plasma membrane side of Sertoli cells in the testis. Our results indicate that isolated mOscp1 is a polyspecific organic solute carrier protein and may be a key molecule for the testicular handling of organic solutes.
Footnotes
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This work was supported in part by Japanese Ministry of Education Sciences, Sports and Culture Grant 16659042.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.107.014795.
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ABBREVIATIONS: SLC, solute carrier; ABC, ATP-binding cassette; CT2, carnitine transporter 2; dCTP, deoxycytidine [5′-α-32P]triphosphate; DHEA-S, dehydroepiandrosterone sulfate; ES, estrone-3-sulfate; 5-FU, 5-fluorouracil; GST, gonad-specific transporter; mOscp1, mouse organic solute carrier protein 1; mNaDC, mouse sodium dicarboxylate cotransporter; 6-MP, 6-mercaptopurine; mPGT, mouse prostaglandin transporter; OAT/Oat, organic anion transporter; OATP/Oatp, organic anion-transporting polypeptide; OCT, organic cation transporter; PAH, p-aminohippurate; PG, prostaglandin; SSC, standard saline citrate; TEA, tetraethylammonium.
- Received January 13, 2007.
- Accepted April 16, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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