Greatly elevated urea excretion after air exposure appears to be carrier mediated in the slender lungfish (Protopterus dolloi).

Under aquatic conditions, Protopterus dolloi is ammoniotelic, excreting only small amounts of urea-N. However, upon return to water after 30 d estivation in air, the lungfish excretes only small amounts of ammonia-N but massive amounts of urea-N. A similar pattern is seen after 21-30 d of terrestrialization, a treatment in which the lungfish is air exposed but kept moist throughout. After both treatments, the time course of urea-N excretion is biphasic with an immediate increase, then a fall, and finally a second larger increase that peaks at about 12 h and may be prolonged for several days thereafter. Urea-N excretion rates during the second peak reach 2,000-6,000 micromol N kg(-1) h(-1), two to three orders of magnitude greater than rates in most fish and comparable only to rates in species known to employ UT-A type facilitated diffusion urea transporters. Divided chamber studies and measurements of the clearance rates of [3H]-PEG-4000 (a glomerular filtration and paracellular diffusion marker) and two structural analogs of urea ([14C]-acetamide and [14C]-thiourea) were performed to characterize the two peaks of urea-N excretion. The smaller first peak was almost equally partitioned between the head (including internal and external gills) and the body compartment (including urinary opening), was accompanied by only a modest increase in [14C]-acetamide clearance equal to that in [14C]-thiourea clearance, and could be accounted for by a large but short-lasting increase in [3H]-PEG-4000 clearance (to about fivefold the terrestrial rate). The delayed, much larger second peak in urea-N excretion represented an elevated efflux into both compartments but occurred mainly (72%) via the body rather than the head region. This second peak was accompanied by a substantial increase in [14C]-acetamide clearance but only a modest further rise in [14C]-thiourea clearance. The acetamide to thiourea permeability ratio was typical of UT-A type transporters in other fish. [3H]-PEG-4000 clearance was stable at this time at about double the terrestrial rate, and excretion rates of urea and its analogs were many fold greater than could be accounted for by [3H]-PEG-4000 clearance. We conclude that the first peak may be explained by elevated urinary excretion and paracellular diffusion across the gills upon resubmergence, while the second peak is attributable to a delayed and prolonged activation of a UT-A type facilitated diffusion mechanism, primarily in the skin and perhaps also in branchial epithelia.