title: Contribution of multidrug resistance-associated proteins (MRPs) to the release of prostanoids from A549 cells.
abstract: Previous studies indicated that several members of the multidrug resistance-associated protein (MRP) family mediate the transport of prostanoids. However, theimportance of MRPs in the release process of prostanoids has not been fully elucidated. In this study, we investigated the contribution of MRPs, including MRP1, MRP2, and MRP4, to the release process of the prostanoids from human lung adenocarcinoma epithelial A549 cells. The extracellular levels of PGE2, PGF2α, and TXB2 (a metabolite of TXA2) were decreased by treatment with MRP inhibitors (dipyridamole, MK571, and probenecid). The studies using membrane vesicle suggest that the effects of the inhibitors were in part by inhibiting MRP4 function. The effects of knockdown of each MRP (MRP1, MRP2, and MRP4) were also investigated. The extracellular levels of PGE2 and PGF2α were significantly decreased after MRP4 knockdown. Our results suggest that MRPs including MRP4 contribute the release process of prostanoids in A549 cells.
authors.affiliation: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Furugen
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Narumi
authors.initials: N
authors.lastname: Shiida
authors.forename: Jiro
authors.initials: J
authors.lastname: Ogura
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*
chemical_list: D051546:Cyclooxygenase 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011453:Prostaglandins
keywords: Multidrug resistance-associated protein; Prostaglandin E(2); Prostaglandin F(2α); Prostanoid release; Thromboxane A(2)