Characterization of an organic anion transport system in a placental cell line.
Transporters within the placenta play a crucial role in the distribution of nutrients and xenobiotics across the maternal-fetal interface. An organic anion transport system was identified on the apical membrane of the rat placenta cell line HRP-1, a model for the placenta barrier. The apical uptake of 3H-labeled organic anion estrone sulfate in HRP-1 cells was saturable (Km = 4.67 microM), temperature and Na+ dependent, Li+ tolerant, and pH sensitive. The substrate specificity of the transport system includes various steroid sulfates, such as beta-estradiol 3,17-disulfate, 17 beta-estradiol 3-sulfate, and dehydroepiandrosterone 3-sulfate (DHEAS) but does not include taurocholate, p-aminohippuric acid (PAH), and tetraethylammonium. Preincubation of HRP-1 cells with 8-bromo-cAMP (a cAMP analog) and forskolin (an adenylyl cyclase activator) acutely stimulated the apical transport activity. This stimulation was further enhanced in the presence of IBMX (a phosphodiesterase inhibitor). Together these data show that the apical membrane of HRP-1 cells expresses an organic anion transport system that is regulated by cellular cAMP levels. This transport system appears to be different from the known taurocholate-transporting organic anion-transporting polypeptides and PAH-transporting organic anion transporters, both of which also mediate the transport of estrone sulfate and DHEAS.
Zhou
Fanfan
F
Department of Pharmaceutics, Rutgers, The State University of New Jersey, 160 Frelinghuysen Rd., Piscataway, NJ 08854, USA.
Tanaka
Kunihiko
K
Soares
Michael J
MJ
You
Guofeng
G
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D027361:Organic Anion Transporters / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism*; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013696:Temperature; D014316:Tritium
D027361:Organic Anion Transporters; D014316:Tritium; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C031555:estradiol sulfate; D004970:Estrone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D008094:Lithium; D012964:Sodium; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C017296:estrone sulfate; D015056:1-Methyl-3-isobutylxanthine