Evidence for sodium-dependent active urea secretion in the deepest subsegment of the rat inner medullary collecting duct

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 IMCD(3)s. 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 mu M 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 IMCD(3)s 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 IMCD(3)s of normal rats which is upregulated in water diuretic rats. This new urea transporter may be a sodium-urea antiporter.