A choline transporter in renal brush-border membrane vesicles: energetics and structural specificity.
A choline transporter in renal brush-border membrane vesicles: energetics and structural specificity.
复制标题
肾刷状缘膜囊泡中的胆碱转运蛋白：能量学和结构特异性。
DOI：
10.1007/bf00233460
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Wunz,TP
中科院分区：
文献类型：
--
作者：
Wright,SH;Wunz,TM;Wunz,TP
胆碱是一种季铵化合物，通常被肾近端小管重吸收，尽管它被公认为肾有机阳离子（OC）分泌途径的底物。通过对兔肾刷状膜囊（BBMV）转运的研究，探讨了胆碱重吸收的基础。虽然向外的H+梯度（pH 6.0in∶7.5out）刺激了肾BBMV中OC/H+交换器模型底物四乙基铵（TEA）的吸收，但对1μ胆碱的吸收没有影响。然而，5毫米的胆碱转移梯度确实驱动了TEA和胆碱的反转运，尽管transtea对胆碱在BBMV中的积累没有影响。20毫米浓度的未标记胆碱阻断了85%的胆碱和TEA的摄取，而20毫米的TEA仅阻断了TEA的摄取。胆碱进入预载1免疫标记胆碱的囊泡的动力学似乎涉及两个饱和运输过程，一个是对胆碱的高亲和力（Ktof为97μm），另一个是低亲和力（Ktof为10 mm），后者可能反映了胆碱与OC/H+交换剂的弱相互作用。内负的电PD刺激了胆碱的摄取速度，并支持胆碱在BBMV中的短暂浓度积累。高亲和转运体对胆碱和密切相关的类似物具有显著的特异性。描述了底物-转运体相互作用的分子决定因素模型。我们得出结论，电致高亲和力途径在肾胆碱重吸收中起核心作用。
Choline is a quaternary ammonium compound that is normally reabsorbed by the renal proximal tubule, despite its acknowledged role as a substrate for the renal organic cation (OC) secretory pathway. The basis for choline reabsorption was examined in studies of transport in rabbit renal brush-border membrane vesicles (BBMV). Although an outwardly directed H+gradient (pH 6.0in∶ 7.5out) stimulated uptake of tetraethylammonium (TEA), a model substrate of the OC/H+exchanger in renal BBMV, it had no effect on uptake of 1μmcholine. A 5 mmtransconcentration gradient of choline did, however, drive countertransport of both TEA and choline, althoughtransTEA had no effect on choline accumulation in BBMV. A 20 mmconcentration of unlabeled choline blocked uptake of both choline and TEA by >85%, whereas 20 mmTEA blocked only TEA uptake. The kinetics of choline uptake into vesicles preloaded with 1 mmunlabeled choline appeared to involve two, saturable transport processes, one of high affinity for choline (Ktof 97μm) and a second of low affinity (Ktof ∼10 mm), the latter presumably reflecting a weak interaction of choline with the OC/H+exchanger. An inside-negative electrical PD stimulated the rate of uptake and supported the transient concentrative accumulation of choline in BBMV. The high affinity transporter showed a marked specificity for choline and closely related analogues. A model of the molecular determinants of substrate-transporter interaction is described. We conclude that the electrogenic high affinity pathway plays a central role in renal reabsorption of choline.