Chou C L, Sands J M, Nonoguchi H, Knepper M A
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Am J Physiol. 1990 Mar;258(3 Pt 2):F486-94. doi: 10.1152/ajprenal.1990.258.3.F486.
The vasopressin-dependent urea permeability of the rat terminal inner medullary collecting duct (IMCD) is much greater than can be explained by lipid-phase permeation or paracellular diffusion, suggesting the presence of vasopressin-stimulated facilitated transport pathway. We used the isolated perfused tubule technique to test whether the urea transport pathway exhibits saturation characteristics consistent with a facilitated pathway. When the luminal urea concentration was varied between 0 and 800 mM (no urea in peritubular bath), the relationship between the urea flux and the luminal concentration was linear with a y-axis intercept that was not significantly different from zero, indicating an absence of saturation in this concentration range. Higher concentrations of urea could not be tested due to technical limitations. However, when thiourea (a urea analogue that shares the urea transport pathway with urea) was substituted for urea in similar experiments, the apparent thiourea permeability fell with increasing thiourea concentration in the range 10-200 mM, indicative of saturation of the urea-thiourea transporter. When the urea concentration was varied in both bath and lumen, the lumen-to-bath urea flux approached a limiting value at 400-500 mM urea, consistent with saturation of the transporter. However, nonspecific inhibition of urea transport by bath urea could not be ruled out in those experiments. We conclude that the urea and thiourea transport pathway in the terminal IMCD exhibits saturation characteristics. However, the urea concentration required to saturate the pathway is apparently high, at least 400-500 mM in one set of experiments and probably greater than 800 mM in another.
大鼠终末内髓集合管（IMCD）中血管升压素依赖性尿素通透性远大于脂相渗透或细胞旁扩散所能解释的程度，这表明存在血管升压素刺激的易化转运途径。我们使用离体灌注肾小管技术来测试尿素转运途径是否表现出与易化途径一致的饱和特性。当管腔尿素浓度在0至800 mM之间变化时（肾小管周围浴液中无尿素），尿素通量与管腔浓度之间的关系呈线性，y轴截距与零无显著差异，表明在此浓度范围内不存在饱和现象。由于技术限制，无法测试更高浓度的尿素。然而，在类似实验中，当用硫脲（一种与尿素共用尿素转运途径的尿素类似物）替代尿素时，在10 - 200 mM范围内，表观硫脲通透性随硫脲浓度增加而下降，表明尿素 - 硫脲转运体饱和。当浴液和管腔中的尿素浓度都变化时，在400 - 500 mM尿素时管腔到浴液的尿素通量接近极限值，这与转运体饱和一致。然而，在这些实验中不能排除浴液中尿素对尿素转运的非特异性抑制作用。我们得出结论，终末IMCD中的尿素和硫脲转运途径表现出饱和特性。然而，使该途径饱和所需的尿素浓度显然很高，在一组实验中至少为400 - 500 mM，在另一组实验中可能大于800 mM。
