Ott R J, Hui A C, Yuan G, Giacomini K M
School of Pharmacy, University of California, San Francisco 94143.
Am J Physiol. 1991 Sep;261(3 Pt 2):F443-51. doi: 10.1152/ajprenal.1991.261.3.F443.
The renal proximal tubule is responsible for the active elimination of organic cations. Studies in brush-border membrane vesicles (BBMV) suggest that active organic cation transport is mediated by an organic cation-proton antiporter. The goals of this study were to determine whether this transporter is expressed in human kidney and to elucidate its characteristics. Transport of the organic cations N1-[3H]methylnicotinamide (NMN) and [14C]tetraethylammonium (TEA) was determined by rapid filtration in BBMV of donor human kidneys. The uptake of NMN and TEA was driven against a concentration gradient by an outwardly directed proton gradient. NMN uptake was inhibited by the organic cations TEA, NMN, quinine, and cimetidine, but was not affected by p-aminohippuric acid, cephalexin, and polyamines. The electroneutral transport of NMN was characterized by a Km of 0.44 +/- 0.07 mM and a Vmax of 24.4 +/- 15.2 pmol.mg protein-1.s-1. The rate of proton efflux from BBMV increased in the presence of an inwardly directed TEA gradient. Preloading BBMV with NMN or TEA trans-stimulated the initial rate of uptake of TEA. Therefore the human proximal tubule expresses an organic cation-proton antiporter in the brush-border membrane. The antiporter is similar to that described in other mammalian species but shows some differences in its transport characteristics.
肾近端小管负责有机阳离子的主动清除。对刷状缘膜囊泡（BBMV）的研究表明，有机阳离子的主动转运由有机阳离子 - 质子反向转运体介导。本研究的目的是确定该转运体是否在人肾中表达，并阐明其特性。通过对供体人肾的BBMV进行快速过滤来测定有机阳离子N1 - [³H]甲基烟酰胺（NMN）和[¹⁴C]四乙铵（TEA）的转运。NMN和TEA的摄取是由外向质子梯度驱动以对抗浓度梯度进行的。NMN的摄取受到有机阳离子TEA、NMN、奎宁和西咪替丁的抑制，但不受对氨基马尿酸、头孢氨苄和多胺的影响。NMN的电中性转运的特征在于Km为0.44±0.07 mM，Vmax为24.4±15.2 pmol·mg蛋白⁻¹·s⁻¹。在存在内向TEA梯度的情况下，BBMV中质子外流速率增加。用NMN或TEA预加载BBMV可反刺激TEA的初始摄取速率。因此，人近端小管在刷状缘膜中表达有机阳离子 - 质子反向转运体。该反向转运体与其他哺乳动物物种中描述的类似，但在其转运特性上存在一些差异。
