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 rat s fed a low-protein diet. To determine whether active urea transport a lso occurs in the deepest IMCD subsegment, the IMCD3, we isolated IMCD s from the base (IMCD1), middle (IMCD2), and tip (IMCD3) regions of th e inner medulla from rats fed a normal protein diet and water ad libit um. 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 sec retion but replacing bath Na+ with NMDG(+) or perfusate Cl- with gluco nate(-) had no effect. Net urea secretion was significantly inhibited by: (a) 250 mu M phloretin (perfusate); (b) 100 nM triamterene (perfus ate); (c) 1 mM ouabain (bath); and (d) cooling the tubule to 23 degree s C. Net urea secretion was significantly stimulated by 10 nM vasopres sin (bath). Next, we perfused IMCD(3)s from water diuretic rats (given food ad libitum) and found a significant, fivefold increase in net ur ea 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-ure a antiporter.