Characterization of prostaglandin E1 transport in rat renal brush-border membrane.
Transport of prostaglandin E(1) (PGE(1)) was investigated in rat renal brush-border membrane vesicles. The uptake of [(3)H]PGE(1) was sensitive to osmosis and temperature. This uptake was saturable and mediated by high-affinity (K(m)=2.1 microM)/low-capacity (V(max)=17.4 pmol/mg protein/30 sec) and low-affinity (K(m)=526.5 microM)/high-capacity (V(max)=1,032.5 pmol/mg protein/30 sec) transport systems. [(3)H]PGE(1) uptake was Na(+)-independent and inhibited by various eicosanoids including PGE(2) and PGF(2alpha). Bromcresol green and sulfobromophthalein, potent inhibitors of prostaglandin transporter (PGT), significantly decreased [(3)H]PGE(1) uptake. Uptake was also inhibited by indomethacin and probenecid, which reportedly have little effect on PGT. Benzylpenicillin and taurocholate decreased the uptake of [(3)H]PGE(1). Like p-[(14)C]aminohippurate (PAH) uptake by vesicles, the uptake of [(3)H]PGE(1) was stimulated by an inside-positive membrane potential, created by applying an inward K(+) gradient and valinomycin. However, the uptake of [(3)H]PGE(1) was not inhibited by PAH, suggesting that PAH and PGE(1) are transported by separate transport systems. [(3)H]PGE(1) uptake was not stimulated by outwardly directed gradients of Cl(-) nor unlabeled PGE(1), indicating that an anion exchanger may not be involved in PGE(1) transport. These findings suggest that the transport of PGE(1) in rat renal brush-border membrane is mediated by specific transport system(s), at least in part, by a potential-sensitive transport system.
Nagai
Junya
J
Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
Taogoshi
Takanori
T
Tokunaga
Akiko
A
Nishikawa
Hiroaki
H
Murakami
Teruo
T
Takano
Mikihisa
M
D000527:Alprostadil / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000378:metabolism / Q000493:pharmacokinetics; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors / Q000502:physiology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D014316:Tritium; D010130:p-Aminohippuric Acid / Q000378:metabolism / Q000493:pharmacokinetics
D015777:Eicosanoids; D049990:Membrane Transport Modulators; D027361:Organic Anion Transporters; C503528:Slco2a1 protein, rat; D014316:Tritium; D000527:Alprostadil; D010130:p-Aminohippuric Acid