Functional analysis of ABCA8, a new drug transporter

We examined the transport capacity in Xenopus laevis oocytes of human EST KIAA0822/ABCAB, a member of the ABC superfamily. Substrates of ABCC2/MRP-2 such as [C-14]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 [C-14]estradiol-beta-glucuronide was ATP-dependent and K-m and V-max values of 30.4 muM and 66.9 pmol/h/egg, respectively, were estimated. The transport of [C-14]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. (C) 2002 Elsevier Science (USA). All rights reserved.