Expression of a renal type I sodium/phosphate transporter (NaPi-1) induces a conductance in Xenopus oocytes permeable for organic and inorganic anions
Expression of a renal type I sodium/phosphate transporter (NaPi-1) induces a conductance in Xenopus oocytes permeable for organic and inorganic anions
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DOI：
10.1073/pnas.93.11.5347
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发表时间：
1996-05-28
影响因子：
11.1
通讯作者：
Lang, F
中科院分区：
文献类型：
--
作者：
Busch, AE;Schuster, A;Lang, F
在示踪实验中，通过表达克隆鉴定了两种不同的分子类型(I和II)的肾脏近端小管刷状边界Na+/P-I共转运蛋白。虽然II型转运蛋白(例如，Napi-2和NaPi3)类似于刷状边界Na+/P-I共转运蛋白的众所周知的特征，但对I型转运蛋白(Napi-1)的性质知之甚少。与II型转运体不同，I型转运体仅在细胞外高P-I浓度(大于或等于3 mM)时才产生电转运。另一方面，Napi-1的表达诱导非洲爪哇卵母细胞的氯离子电导，这一作用可被氯离子通道阻断剂[5-硝基-2-(3-苯丙氨基)苯甲酸(NPPB)>；尼氟米酸；>；4，4‘-二异硫氰基二苯乙烯-2，2’-二磺酸]所抑制。此外，有机阴离子苯酚红、青霉素(青霉素G)和丙磺舒对氯离子电导有抑制作用。这些有机阴离子在无氯离子的情况下产生外向电流。在示踪研究中，我们观察到青霉素摄取的K-m为0.22 mm；NPPB和尼氟米酸抑制了青霉素的摄取。这些发现表明，I型Na+/P-I共转运体也是一种新型的阴离子通道，不仅可以通透Cl-，还可以通透有机阴离子。这种顶端阴离子通道可能在氯离子的运输和阴离子异物的排泄中发挥重要作用。
Two distinct molecular types (I and II) of renal proximal tubular brush border Na+/P-i cotransporters have been identified by expression cloning on the basis of their capacity to induce Na+-dependent P-i influx in tracer experiments. Whereas the type II transporters (e.g., NaPi-2 and NaPi3) resemble well known characteristics of brush border Na+/P-i cotransport, little is known about the properties of the type I transporter (NaPi-1). In contrast to type II, type I transporters produced electrogenic transport only at high extracellular P-i concentrations (greater than or equal to 3 mM). On the other hand, expression of NaPi-1 induced a Cl- conductance in Xenopus laevis oocytes, which was inhibited by Cl- channel blockers [5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) > niflumic acid >> 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid]. Further, the Cl- conductance was inhibited by the organic anions phenol red, benzylpenicillin (penicillin G), and probenecid. These organic anions induced outwardly directed currents in the absence of Cl-. In tracer studies, we observed uptake of benzylpenicillin with a K-m of 0.22 mM; benzylpenicillin uptake was inhibited by NPPB and niflumic acid. These findings suggest that the type I Na+/P-i cotransporter functions also as a novel type of anion channel permeable not only for Cl- but also for organic anions. Such an apical anion channel could serve an important role in the transport of Cl- and the excretion of anionic xenobiotics.