Zerbini G, Maestroni A, Mangili R, Pozza G
Division of Medicine, Scientific Institute San Raffaele, University of Milan, Italy.
J Am Soc Nephrol. 1998 Dec;9(12):2203-11. doi: 10.1681/ASN.V9122203.
Erythrocyte Na+-Li+ countertransport shows an increased activity in essential hypertension and diabetic nephropathy, but its nature remains unknown. This amiloride-insensitive membrane transport may not be a mode of operation of the amiloride-sensitive NHE1, the only Na+-H+ exchange isoform found in human erythrocytes. Whether an independent, although unknown, amiloride-insensitive isoform mediates Na+-Li+ countertransport is unclear. Na+-H+ exchange activity was measured in acid-loaded erythrocytes. Dimethylamiloride, a specific inhibitor of Na+-H+ exchange and phloretin, a known inhibitor of Na+-Li+ countertransport, gave a reduction in H+-driven Na+ influx (by 31 and 37%, respectively). This effect was additive, and a 66% reduction in H+-driven Na+ influx was found in the presence of both inhibitors. Internal acidification, a stimulus for Na+-H+ exchange, enhanced Na+-Li+ countertransport activity (from 287 +/- 55 to 1213 +/- 165 micromol x Lcell(-1) h(-1), mean +/- SEM, P = 0.003). This transport remained sensitive to phloretin under both conditions. Conversely, external acidification decreased Na+-Li+ countertransport activity (as expected for a Na+-H+ exchanger). Competition between internal H+ and Li+ or Na+ for a common binding site was present. Finally, similar kinetic parameters for external Na+ characterized Na+-Li+ countertransport and the phloretin-sensitive component of H+-driven Na+ influx. These findings suggest that both Na+-Li+ countertransport and the amiloride-insensitive, phloretin-sensitive component of H+-driven Na+ influx can be mediated by a previously unrecognized novel amiloride-insensitive Na+-H+ exchange isoform in human erythrocytes.
红细胞钠-锂逆向转运在原发性高血压和糖尿病肾病中活性增加，但其本质仍不清楚。这种对阿米洛利不敏感的膜转运可能不是对阿米洛利敏感的NHE1（人类红细胞中唯一发现的钠-氢交换亚型）的运作模式。是否存在一种独立的、尽管未知的对阿米洛利不敏感的亚型介导钠-锂逆向转运尚不清楚。在酸负荷的红细胞中测量了钠-氢交换活性。二甲基阿米洛利（一种钠-氢交换的特异性抑制剂）和根皮素（一种已知的钠-锂逆向转运抑制剂）使氢驱动的钠内流分别减少了31%和37%。这种作用是相加的，在两种抑制剂同时存在时，氢驱动的钠内流减少了66%。内部酸化是钠-氢交换的刺激因素，增强了钠-锂逆向转运活性（从287±55增加到1213±165微摩尔×L细胞⁻¹小时⁻¹，平均值±标准误，P = 0.003）。在两种情况下，这种转运对根皮素仍敏感。相反，外部酸化降低了钠-锂逆向转运活性（正如钠-氢交换器所预期的那样）。内部氢离子与锂离子或钠离子之间存在对共同结合位点的竞争。最后，外部钠离子的相似动力学参数表征了钠-锂逆向转运和氢驱动的钠内流中对根皮素敏感的成分。这些发现表明，钠-锂逆向转运以及氢驱动的钠内流中对阿米洛利不敏感、对根皮素敏感的成分可能由人类红细胞中一种先前未被认识的新型对阿米洛利不敏感的钠-氢交换亚型介导。
