Transport of prostaglandin E1 across rat erythrocyte membrane.
In this study erythrocyte transport of prostaglandin E1 (PGE1) was investigated by employing inside-out membrane vesicles prepared from rat erythrocytes. The uptake of [3H]PGE1 in the presence of ATP was significantly higher than that of AMP, suggesting the involvement of an ATP-dependent efflux system in PGE1 transport across the erythrocyte membrane. Coincubation of glutathione with ATP further stimulated the uptake of [3H]PGE1. The uptake of [3H]PGE1 in the presence of ATP and glutathione was temperature-sensitive, and various eicosanoids including PGE2 and PGF2alpha decreased the uptake. Multidrug resistance-associated protein (MRP) 4 substrates/inhibitors including methotrexate, indomethacin, taurocholic acid and indocyanine green significantly inhibited [3H]PGE1 uptake. Western blot analysis revealed that Mrp4 is expressed in rat erythrocyte membrane. These results suggest that the release of PGE1 from the erythrocyte into the blood circulation may be mediated by ATP-dependent efflux pump(s) such as Mrp4.
Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Takanori
T
Taogoshi
Junya
J
Nagai
Ryoko
R
Yumoto
Mikihisa
M
Takano
D000255:Adenosine Triphosphate / Q000502:physiology; D000527:Alprostadil / Q000037:antagonists & inhibitors / Q000097:blood*; D000818:Animals; D001693:Biological Transport, Active; D015153:Blotting, Western; D015777:Eicosanoids / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D015151:Immunoblotting; D066298:In Vitro Techniques; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats; D013696:Temperature; D022161:Transport Vesicles / Q000378:metabolism
D000255:Adenosine Triphosphate; D000527:Alprostadil; D015777:Eicosanoids; D005978:Glutathione; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011448:Prostaglandin Antagonists; C489542:Abcc4 protein, rat