Functional analysis of ABCA8, a new drug transporter.
We examined the transport capacity in Xenopus laevis oocytes of human EST KIAA0822/ABCA8, a member of the ABC superfamily. Substrates of ABCC2/MRP-2 such as [14C]estradiol-beta-glucuronide, taurocholate, and LTC4, and of organic anion transporter (OAT), such as para-aminohippuric acid, ochratoxin-A, were significantly accumulated while tetraethylammonium and doxorubicin were not. The transport of [14C]estradiol-beta-glucuronide was ATP-dependent and K(m) and V(max) values of 30.4microM and 66.9pmol/h/egg, respectively, were estimated. The transport of [14C]estradiol-beta-glucuronide was inhibited by substrates/inhibitors of ABCC2/MRP-2, but not by those of the organic cation transporter and multidrug resistance protein (MDR)-1. KIAA0822/ABCA8 possesses two ATP-binding sites and fourteen transmembrane domains. Northern blot analysis revealed expression in most organs, especially in heart, skeletal muscle, and liver. Thus, ABCA8 is a new member of the xenobiotic transporter ABC-subfamily.
Tsuruoka
Shuichi
S
Department of Clinical Pharmacology, Jichi Medical School, 3311 Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0498, Japan. tsuru@jichi.ac.jp
Ishibashi
Kenichi
K
Yamamoto
Hisashi
H
Wakaumi
Michi
M
Suzuki
Makoto
M
Schwartz
George J
GJ
Imai
Masashi
M
Fujimura
Akio
A
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D000089762:Multidrug Resistance-Associated Protein 2; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013379:Substrate Specificity; D014018:Tissue Distribution; D015262:Xenobiotics / Q000494:pharmacology; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
C468121:ABCA8 protein, Xenopus; C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D012333:RNA, Messenger; D015262:Xenobiotics; D029867:Xenopus Proteins; C025483:estradiol-17 beta-glucuronide; D004958:Estradiol