Kim K R, Kim G C, Choi J S, Ahn D W, Park Y S
Department of Physiology, Kosin Medical College, Pusan, Korea.
Toxicol Appl Pharmacol. 1998 Apr;149(2):144-9. doi: 10.1006/taap.1998.8374.
To evaluate the effect of cadmium intoxication on renal transport systems for organic anions and cations, transport of p-aminohippurate (PAH) and tetraethylammonium (TEA) were studied in renal cortical plasma membrane vesicles isolated from cadmium-intoxicated rats. Cadmium intoxication was induced by daily injections of CdCl2 (2 mg Cd/kg.day sc) for 2-3 weeks. Renal plasma membrane vesicles were prepared by Percoll gradient centrifugation and magnesium precipitation method. Vesicular uptake of substrate was determined by rapid filtration technique using Millipore filter. The cadmium treatment resulted in a marked attenuation of Na(+)-dependent, alpha-ketoglutarate (alpha KG)-driven PAH uptake in the basolateral membrane vesicle (BLMV), and this was due to a reduction in Vmax and not K(m). The Na(+)-alpha KG symport activity of the BLMV was not affected by 2-week cadmium treatment, but it was significantly inhibited by 3-week cadmium treatment. On the other hand, the alpha KG-PAH antiport activity of the BLMV appeared to be markedly suppressed in 2-week as well as 3-week cadmium-treated animals. The cadmium treatment inhibited the proton gradient-dependent TEA transport in the brush-border membrane vesicle (BBMV), and this was associated with a reduction in Vmax with no change in K(m). These results indicate that cadmium exposures may impair the capacities for organic anion transport in the proximal tubular basolateral membrane and organic cation transport in the luminal membrane. The cadmium effect on organic anion transport is attributed mainly to an inhibition of dicarboxylate-organic anion antiport system.
为评估镉中毒对有机阴离子和阳离子肾脏转运系统的影响，对从镉中毒大鼠分离的肾皮质质膜囊泡中对氨基马尿酸（PAH）和四乙铵（TEA）的转运进行了研究。通过每天皮下注射CdCl2（2 mg镉/千克·天），持续2 - 3周来诱导镉中毒。采用Percoll梯度离心和镁沉淀法制备肾质膜囊泡。使用微孔滤膜通过快速过滤技术测定底物的囊泡摄取。镉处理导致基底外侧膜囊泡（BLMV）中依赖Na(+)、α - 酮戊二酸（αKG）驱动的PAH摄取显著减弱，这是由于Vmax降低而非K(m)降低所致。2周镉处理未影响BLMV的Na(+) - αKG同向转运活性，但3周镉处理使其显著受到抑制。另一方面，在2周和3周镉处理的动物中，BLMV的αKG - PAH反向转运活性似乎均明显受到抑制。镉处理抑制了刷状缘膜囊泡（BBMV）中质子梯度依赖性的TEA转运，这与Vmax降低而K(m)不变有关。这些结果表明，镉暴露可能损害近端肾小管基底外侧膜中有机阴离子转运能力以及管腔膜中有机阳离子转运能力。镉对有机阴离子转运的影响主要归因于对二羧酸 - 有机阴离子反向转运系统的抑制。
