Chen R, Pan B F, Sakurai M, Nelson J A
Department of Experimental Pediatrics and Graduate School of Biomedical Sciences, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Am J Physiol. 1999 Feb;276(2):F323-8. doi: 10.1152/ajprenal.1999.276.2.F323.
Renal secretion of organic cations and anions are pleiotropic, active processes in mammals. Some nucleosides such as deoxyadenosine (dAdo), 2-chlorodeoxyadenosine, and azidothymidine are secreted by human and rodent kidneys. Previous work (J. A. Nelson, J. F. Kuttesch, Jr., and B. H. Herbert. Biochemical Pharmacology 32: 2323-2327, 1983) indicated a role for the classic organic cation transporter (OCT) in the secretion of the dAdo analog, 2'-deoxytubercidin, by mouse kidney. Using [14C]tetraethylammonium bromide ([14C]TEA) as a substrate, we tested several renal cell lines for a nucleoside-sensitive OCT. American opossum kidney proximal tubule cells (OK) express a cimetidine-sensitive and metabolic-dependent ability to efflux TEA. Other classic OCT inhibitors and several nucleosides also inhibit TEA efflux by these cells in a manner reflecting structural specificity for the carrier. Inhibition of OCT by nucleosides is not a universal feature of OCTs, since TEA transport mediated by cloned rat kidney OCT2 in the Xenopus laevis oocyte system was not inhibited by the same nucleosides. In conclusion, OK cells appear to possess an OCT that may also transport some nucleosides by a novel carrier.
在哺乳动物中，肾脏对有机阳离子和阴离子的分泌是多效性的主动过程。一些核苷，如脱氧腺苷（dAdo）、2-氯脱氧腺苷和叠氮胸苷，可由人和啮齿动物的肾脏分泌。先前的研究（J.A.尼尔森、J.F.库特施、小B.H.赫伯特。《生化药理学》32:2323-2327，1983）表明，经典有机阳离子转运体（OCT）在小鼠肾脏分泌dAdo类似物2'-脱氧结核菌素中起作用。我们以[14C]溴化四乙铵（[14C]TEA）为底物，测试了几种肾细胞系中对核苷敏感的OCT。美洲负鼠肾近端小管细胞（OK）表现出对西咪替丁敏感且依赖代谢的TEA外排能力。其他经典的OCT抑制剂和几种核苷也以反映载体结构特异性的方式抑制这些细胞的TEA外排。核苷对OCT的抑制并非OCT的普遍特征，因为非洲爪蟾卵母细胞系统中克隆的大鼠肾脏OCT2介导的TEA转运不受相同核苷的抑制。总之，OK细胞似乎拥有一种OCT，它也可能通过一种新型载体转运一些核苷。
