Kato A, Sands J M
Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Clin Invest. 1998 Jan 15;101(2):423-8. doi: 10.1172/JCI1420.
Active reabsorption of urea appears in the initial IMCD (IMCD1) of rats fed a low-protein diet. To determine whether active urea transport also occurs in the deepest IMCD subsegment, the IMCD3, we isolated IMCDs from the base (IMCD1), middle (IMCD2), and tip (IMCD3) regions of the inner medulla from rats fed a normal protein diet and water ad libitum. IMCDs were perfused with identical perfusate and bath solutions. A significant rate of net urea secretion was present only in IMCD3s. Replacing perfusate Na+ with NMDG+ reversibly inhibited net urea secretion but replacing bath Na+ with NMDG+ or perfusate Cl- with gluconate- had no effect. Net urea secretion was significantly inhibited by: (a) 250 microM phloretin (perfusate); (b) 100 nM triamterene (perfusate); (c) 1 mM ouabain (bath); and (d) cooling the tubule to 23 degrees C. Net urea secretion was significantly stimulated by 10 nM vasopressin (bath). Next, we perfused IMCD3s from water diuretic rats (given food ad libitum) and found a significant, fivefold increase in net urea secretion. In summary, we identified a secondary active, secretory urea transport process in IMCD3s of normal rats which is upregulated in water diuretic rats. This new urea transporter may be a sodium- urea antiporter.
在喂食低蛋白饮食的大鼠的初始内髓集合管（IMCD1）中出现尿素的主动重吸收。为了确定在最深的IMCD亚段即IMCD3中是否也发生主动尿素转运，我们从自由饮水且喂食正常蛋白饮食的大鼠的内髓基部（IMCD1）、中部（IMCD2）和尖端（IMCD3）区域分离出IMCD。用相同的灌注液和浴液灌注IMCD。仅在IMCD3中存在显著的净尿素分泌率。用NMDG⁺替代灌注液中的Na⁺可逆地抑制净尿素分泌，但用NMDG⁺替代浴液中的Na⁺或用葡萄糖酸盐⁻替代灌注液中的Cl⁻则没有影响。净尿素分泌受到以下因素的显著抑制：（a）250微摩尔的根皮素（灌注液）；（b）100纳摩尔的氨苯蝶啶（灌注液）；（c）1毫摩尔的哇巴因（浴液）；以及（d）将小管冷却至23摄氏度。10纳摩尔的血管加压素（浴液）显著刺激净尿素分泌。接下来，我们灌注了水利尿大鼠（自由进食）的IMCD3，发现净尿素分泌显著增加了五倍。总之，我们在正常大鼠的IMCD3中鉴定出一种继发性主动分泌性尿素转运过程，该过程在水利尿大鼠中上调。这种新的尿素转运体可能是一种钠 - 尿素反向转运体。
