Linder G, Foulkes E C
Environ Res. 1985 Feb;36(1):241-7. doi: 10.1016/0013-9351(85)90021-0.
A modified clearance technique originally developed for the intact rabbit was adapted for use in the intact rat; it permits measurement of maximum tubular capacity (Tm) and half-saturation constant (KM) without the need for high systemic plasma levels and long equilibrating infusions of the solute under study. In this manner, Tm and KM for aspartate reabsorption were determined. Subsequently, we compared these kinetics constants to renal aspartate Tm and KM values in the literature derived from single tubule studies, and analyzed the nephrotoxicity of nickel and cadmium. Aspartate KM and Tm in the intact rat were 6.1 mM and 5.8 mumole/g cortex/min respectively; in contrast, work with single tubules led to KM aspartate of 0.1 mM and Tm aspartate of 20.0 mumole/g cortex/min. The discrepancy between the two sets of results reemphasizes the difficulty in extrapolating from single tubules to intact kidney; presumably tubular heterogeneity accounts for these differences. Aspartate reabsorption was also measured in rats injected intraperitoneally with 20 mumole nickel or cadmium/kg body weight 36 to 40 hr previously. At renal nickel or cadmium concentrations of approximately 10 micrograms/g kidney glomerular filtration rate and aspartate Tm were significantly decreased while aspartate KM was not affected. The effects of the metals resemble a noncompetitive type of inhibition of aspartate reabsorption.
一种最初为完整兔体开发的改良清除技术被应用于完整大鼠；它能够在无需高全身血浆水平以及长时间平衡输注受试溶质的情况下，测量最大肾小管转运能力（Tm）和半饱和常数（KM）。通过这种方式，测定了天冬氨酸重吸收的Tm和KM。随后，我们将这些动力学常数与文献中来自单肾小管研究的肾天冬氨酸Tm和KM值进行了比较，并分析了镍和镉的肾毒性。完整大鼠中天冬氨酸的KM和Tm分别为6.1 mM和5.8微摩尔/克皮质/分钟；相比之下，单肾小管研究得出的天冬氨酸KM为0.1 mM，天冬氨酸Tm为20.0微摩尔/克皮质/分钟。两组结果之间的差异再次强调了从单肾小管推断到完整肾脏的困难；推测肾小管的异质性是造成这些差异的原因。还对36至40小时前腹腔注射20微摩尔镍或镉/千克体重的大鼠进行了天冬氨酸重吸收的测量。当肾脏中镍或镉的浓度约为10微克/克肾脏时，肾小球滤过率和天冬氨酸Tm显著降低，而天冬氨酸KM未受影响。这些金属的作用类似于对天冬氨酸重吸收的非竞争性抑制类型。
