The dopamine precursor L-dihydroxyphenylalanine is transported by the amino acid transporters rBAT and LAT2 in renal cortex.
The dopamine precursor L-dihydroxyphenylalanine is transported by the amino acid transporters rBAT and LAT2 in renal cortex.
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DOI：
10.1152/ajprenal.00237.2003
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发表时间：
2004-07
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影响因子：
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通讯作者：
Henry Quiñones;Roberto Collazo;O. Moe
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作者：
Henry Quiñones;Roberto Collazo;O. Moe
肾内自分泌-旁分泌多巴胺（DA）系统对Na（+）稳态至关重要。从肾小球滤液和血浆摄取l-二羟基苯丙氨酸（l-DOPA）为肾近端小管生成DA提供了底物。负责近端小管左旋多巴摄取的转运蛋白尚未被表征。将肾皮质多聚a(+) RNA注射到非洲爪蟾卵母细胞中，以时间和剂量依赖的方式诱导左旋多巴摄取，在毫摩尔和微摩尔范围内呈双相K(m)s，与向内的Na（+）、K（+）或H（+）梯度无关，表明存在低亲和力和高亲和力的左旋多巴载体。来自两种氨基酸转运体的互补RNA产生的l-DOPA摄取显著高于注入水的对照rBAT/b(0,+)AT二聚体（rBAT）和LAT2/ 4f2二聚体（LAT2）。与肾皮质多聚a（+）相比，rBAT和LAT2的l-DOPA动力学分别在K(m)s的微摩尔和毫摩尔范围内表现为经典的Michaelis-Menton动力学。序列特异性的rBAT或LAT2 （AS）反义寡核苷酸可抑制rBAT和LAT2 crna诱导的左旋多巴转运和皮质多聚a（+）诱导的精氨酸和苯丙氨酸转运。然而，相同的ASs仅部分阻断poly-A（+）诱导的l-DOPA转运。在培养的肾细胞中，沉默rBAT的抑制RNA （siRNA）显著抑制左旋多巴的摄取。我们得出结论，rBAT和LAT2可以分别介导顶端和基底外侧左旋多巴摄取到近端小管。肾皮质中存在其他左旋多巴转运机制，但仍有待确定。
The intrarenal autocrine-paracrine dopamine (DA) system is critical for Na(+) homeostasis. l-Dihydroxyphenylalanine (l-DOPA) uptake from the glomerular filtrate and plasma provides the substrate for DA generation by the renal proximal tubule. The transporter(s) responsible for proximal tubule l-DOPA uptake has not been characterized. Renal cortical poly-A(+) RNA injected into Xenopus laevis oocytes induced l-DOPA uptake in a time- and dose-dependent fashion with biphasic K(m)s in the millimolar and micromolar range and independent of inward Na(+), K(+), or H(+) gradients, suggesting the presence of low- and high-affinity l-DOPA carriers. Complementary RNA from two amino acid transporters yielded l-DOPA uptake significantly above water-injected controls the rBAT/b(0,+)AT dimer (rBAT) and the LAT2/4F2 dimer (LAT2). In contradistinction to renal cortical poly-A(+), l-DOPA kinetics of rBAT and LAT2 showed classic Michaelis-Menton kinetics with K(m)s in the micromolar and millimolar range, respectively. Sequence-specific antisense oligonucleotides to rBAT or LAT2 (AS) caused inhibition of rBAT and LAT2 cRNA-induced l-DOPA transport and cortical poly-A(+)-induced arginine and phenylalanine transport. However, the same ASs only partially blocked poly-A(+)-induced l-DOPA transport. In cultured kidney cells, silencing inhibitory RNA (siRNA) to rBAT significantly inhibited l-DOPA uptake. We conclude that rBAT and LAT2 can mediate apical and basolateral l-DOPA uptake into the proximal tubule, respectively. Additional l-DOPA transport mechanisms exist in the renal cortex that remain to be identified.