鸟类基底外侧膜囊泡中的尿酸盐/α-酮戊二酸交换

Department of Pharmacology, State University of New York, Upstate Medical University, 766 Irving Avenue, Syracuse, NY 13210, USA.

Am J Physiol Cell Physiol. 2002 Oct;283(4):C1144-54. doi: 10.1152/ajpcell.00379.2001.

Membrane transport pathways for transcellular secretion of urate across the proximal tubule were investigated in avian kidney. The presence of coupled urate/alpha-ketoglutarate exchange was investigated in basolateral membrane vesicles (BLMV) by [(14)C]urate and [alpha-(3)H]ketoglutarate flux measurements. An inward Na gradient induced accumulation of alpha-ketoglutarate of sufficient magnitude to suggest a Na-dicarboxylate cotransporter. An inward Na gradient also induced concentrative accumulation of urate in the presence of alpha-ketoglutarate but not in its absence, suggesting urate/alpha-ketoglutarate exchange. alpha-Ketoglutarate-dependent stimulation of urate uptake was not observed in brush-border membrane vesicles. An outward urate gradient induced concentrative accumulation of alpha-ketoglutarate. alpha-Ketoglutarate-coupled urate uptake was specific for alpha-ketoglutarate, Cl dependent, and insensitive to membrane potential. alpha-Ketoglutarate-coupled urate uptake was inhibited by increasing p-aminohippurate (PAH) concentrations, and alpha-ketoglutarate-coupled PAH uptake was observed. alpha-Ketoglutarate-coupled PAH uptake was inhibited by increasing urate concentrations, and an outward urate gradient induced concentrative accumulation of PAH. These results suggest a Cl-dependent, alpha-ketoglutarate-coupled anion exchange mechanism as a pathway for active urate uptake across the basolateral membrane of urate-secreting proximal tubule cells.

在禽肾中研究了尿酸经近端小管进行跨细胞分泌的膜转运途径。通过[（14）C]尿酸和[α-（3）H]酮戊二酸通量测量，在基底外侧膜囊泡（BLMV）中研究了尿酸/α-酮戊二酸耦合交换的存在情况。内向的钠梯度诱导了足够量的α-酮戊二酸积累，提示存在钠-二羧酸共转运体。在存在α-酮戊二酸的情况下，内向的钠梯度也诱导了尿酸的浓缩积累，但在不存在α-酮戊二酸时则未观察到，这表明存在尿酸/α-酮戊二酸交换。在刷状缘膜囊泡中未观察到α-酮戊二酸依赖性的尿酸摄取刺激。外向的尿酸梯度诱导了α-酮戊二酸的浓缩积累。α-酮戊二酸耦合的尿酸摄取对α-酮戊二酸具有特异性，依赖于氯离子，且对膜电位不敏感。α-酮戊二酸耦合的尿酸摄取受到对氨基马尿酸（PAH）浓度增加的抑制，并且观察到了α-酮戊二酸耦合的PAH摄取。α-酮戊二酸耦合的PAH摄取受到尿酸浓度增加的抑制，并且外向的尿酸梯度诱导了PAH的浓缩积累。这些结果提示存在一种依赖于氯离子、α-酮戊二酸耦合的阴离子交换机制，作为尿酸分泌性近端小管细胞基底外侧膜上主动摄取尿酸的途径。