Fenton Robert A, Chou Chung-Lin, Sowersby Holly, Smith Craig P, Knepper Mark A
Laboratory of Kidney and Electrolyte Metabolism, National Hearth, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA, and Faculty of Life Sciences, University of Manchester, UK.
Am J Physiol Renal Physiol. 2006 Jul;291(1):F148-54. doi: 10.1152/ajprenal.00348.2005. Epub 2006 Feb 14.
The Gamble phenomenon (initially described over 70 years ago as "an economy of water in renal function referable to urea") suggested that urea plays a special role in the urinary concentrating mechanism and that the concentrating mechanism depends in some complex way on an interaction between NaCl and urea. In this study, the role of collecting duct urea transporters in the Gamble phenomenon was investigated in wild-type mice and mice in which the inner medulla collecting duct (IMCD) facilitative urea transporters, UT-A1 and UT-A3, had been deleted (UT-A1/3-/- mice). The general features of the Gamble phenomenon were confirmed in wild-type mice, namely 1) the water requirement for the excretion of urea is less than for the excretion of an osmotically equivalent amount of NaCl; and 2) when fed various mixtures of urea and salt in the diet, less water is required for the excretion of the two substances together than the amount of water needed for the excretion of the two substances separately. In UT-A1/3-/- mice both of these elements of the phenomenon were absent, indicating that IMCD urea transporters play a central role in the Gamble phenomenon. A titration study in which wild-type mice were given progressively increasing amounts of urea showed that the ability of the kidney to reabsorb urea was saturable, resulting in osmotic diuresis above excretion rates of approximately 6,000 microosmol/day. In the same titration experiments, when increasing amounts of NaCl were added to the diet, mice were unable to increase urinary NaCl concentrations to >420 mM, resulting in osmotic diuresis at NaCl excretion rates of approximately 3,500 microosmol/day. Thus both urea and NaCl can induce osmotic diuresis when large amounts are given, supporting the conclusion that the decrease in water excretion with mixtures of urea and NaCl added to the diet (compared with pure NaCl or urea) is due to the separate abilities of urea and NaCl to induce osmotic diuresis, rather than to any specific interaction of urea transport and NaCl transport at an epithelial level.
甘布尔现象（最初在70多年前被描述为“肾功能中与尿素相关的节水现象”）表明，尿素在尿液浓缩机制中发挥着特殊作用，且该浓缩机制在某种复杂的方式上依赖于氯化钠和尿素之间的相互作用。在本研究中，在野生型小鼠以及敲除了髓质集合管（IMCD）易化尿素转运体UT-A1和UT-A3的小鼠（UT-A1/3-/-小鼠）中，研究了集合管尿素转运体在甘布尔现象中的作用。野生型小鼠中证实了甘布尔现象的一般特征，即：1）排泄尿素所需的水量少于排泄等渗量氯化钠所需的水量；2）当在饮食中给予各种尿素和盐的混合物时，同时排泄这两种物质所需的水量少于分别排泄这两种物质所需的水量。在UT-A1/3-/-小鼠中，该现象的这两个要素均不存在，表明IMCD尿素转运体在甘布尔现象中起核心作用。一项对野生型小鼠给予逐渐增加量尿素的滴定研究表明，肾脏重吸收尿素的能力是可饱和的，在排泄率约为6,000微渗摩尔/天时会导致渗透性利尿。在相同的滴定实验中，当饮食中添加越来越多的氯化钠时，小鼠无法将尿中氯化钠浓度提高到>420 mM，在氯化钠排泄率约为3,500微渗摩尔/天时会导致渗透性利尿。因此，大量给予尿素和氯化钠时均可诱导渗透性利尿，支持以下结论：饮食中添加尿素和氯化钠的混合物时水排泄量的减少（与纯氯化钠或尿素相比）是由于尿素和氯化钠各自诱导渗透性利尿的能力，而非尿素转运和氯化钠转运在上皮水平的任何特定相互作用。
