Isolation and functional characterization of a novel organic solute carrier protein, hOSCP1.
We succeeded in isolating a novel organic solute carrier from a human placenta cDNA library. The isolated cDNA consisted of 1137 base pairs that encoded a 379-amino acid protein, hOSCP1. Northern blot and reverse transcription PCR analyses revealed that the hOSCP1 mRNA is expressed in the placenta and testis and weakly expressed in the thymus and small intestine. When expressed in Xenopus laevis oocytes, hOSCP1 mediated the high affinity transport of p-aminohippurate (PAH) (K(m) = 35.0 +/- 7.5 microm) and tetraethylammonium (K(m) = 62.3 +/- 12.2 microm) in a sodium-independent manner. However, the hOSCP1-expressing oocyte did not mediate the transport of L-carnitine. The transport of PAH by hOSCP1 was sensitive to pH, but the tetraethylammonium was not transported at the high pH examined. hOSCP1 transported prostaglandin E(2), prostaglandin F(2alpha), estrone sulfate, glutarate, L-leucine, L-ascorbic acid, and tetracycline. Thus, hOSCP1 also showed broad substrate specificity. A wide range of structurally unrelated organic compounds inhibited the hOSCP1-mediated PAH uptake. Immunohistochemical analysis revealed that the hOSCP1 protein is localized in the basal membrane of the syncytiotrophoblast in the human placenta. Our results suggest that hOSCP1 is a novel polyspecific organic solute carrier protein responsible for drug clearance from the human placenta.
Kobayashi
Yasuna
Y
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Shinagawa-ku, Tokyo, Japan.
Shibusawa
Akiko
A
Saito
Hironori
H
Ohshiro
Naomi
N
Ohbayashi
Masayuki
M
Kohyama
Noriko
N
Yamamoto
Toshinori
T
D000595:Amino Acid Sequence; D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry; D001692:Biological Transport; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004970:Estrone / Q000031:analogs & derivatives / Q000737:chemistry; D005260:Female; D015723:Gene Library; D016147:Genes, Tumor Suppressor; D005977:Glutarates / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000737:chemistry; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010802:Phylogeny; D010920:Placenta / Q000378:metabolism; D018075:RNA, Complementary / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000737:chemistry; D013379:Substrate Specificity; D013737:Testis / Q000378:metabolism; D013752:Tetracycline / Q000737:chemistry; D019789:Tetraethylammonium / Q000737:chemistry; D013950:Thymus Gland / Q000378:metabolism; D014018:Tissue Distribution; D014327:Trophoblasts / Q000378:metabolism; D014982:Xenopus laevis / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D018076:DNA, Complementary; D005977:Glutarates; D026901:Membrane Transport Proteins; C479458:OSCP1 protein, human; D018075:RNA, Complementary; D012333:RNA, Messenger; D004970:Estrone; D019789:Tetraethylammonium; D012964:Sodium; D015237:Dinoprost; D013752:Tetracycline; D007930:Leucine; D015232:Dinoprostone; D001205:Ascorbic Acid; C017296:estrone sulfate; D010130:p-Aminohippuric Acid