Isolation and characterization of polyspecific mouse organic solute carrier protein 1 (mOscp1).
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) (K(m) = 18.8 +/- 4.1 microM) 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.
Kobayashi
Yasuna
Y
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Tsuchiya
Ayumi
A
Hayashi
Tomofumi
T
Kohyama
Noriko
N
Ohbayashi
Masayuki
M
Yamamoto
Toshinori
T
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003520:Cyclophosphamide / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D015723:Gene Library; D005977:Glutarates / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D026901:Membrane Transport Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008845:Microinjections; D008969:Molecular Sequence Data; D009865:Oocytes; D011339:Probenecid / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D012708:Sertoli Cells / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D014982:Xenopus laevis; D010130:p-Aminohippuric Acid / Q000378:metabolism
D005977:Glutarates; D026901:Membrane Transport Proteins; C521274:Oscp1 protein, mouse; D012333:RNA, Messenger; D019314:Dehydroepiandrosterone Sulfate; D003520:Cyclophosphamide; D012964:Sodium; D011339:Probenecid; D010130:p-Aminohippuric Acid