Active cellular transport of urea by frog renal tubules.

P KEVIOUS studies have shown that, in the frog, urea is excreted in part by tubular activity. Marshall and Crane in their classic paper on the secretory function of renal tubules (I) emphasized that urea ex-cretion in frogs differed from that in mammals and resembled phenol red elimination in frogs and mammals in that its excretory efficiency (U/P ratio) was depressed as plasma concentrations were raised. This was interpreted as indicating a saturation of the secretory cells. They concluded that this secretory activity was confined to the proximal convoluted tu-bules because both urea and phenol red were found to be more concentrated in the dorsal part of the frog's kidney, which contains the proximal segments, than in the ventral. Later JMarshall showed that urea concentrations in urine may exceed those simultaneously in plasma by as much as zo-3+fold, whereas xilose, only slightly reabsorbed, had U/P ratios which never exceeded 3.0 (2). Walker and Hudson showed in tubular puncture studies that, in contrast to Necturus, the frog concentrates urea to a degree greatly exceeding that of glucose in phlorizinized animals. They concurred with Marshall that some urea is excreted by tubular activity (3). Schmidt-Nielsen and Forster found that urea clearances were 4-110 times higher than simultaneous glomerular filtration rates in bullfrogs. p-Aminohippurate (PAH) clearances, which measured renal plasma flows, were approximately three times higher than simultaneous urea clearances (4, 5). The studies reported here were undertaken to determine to what extent the urea excre-tory process exhibits those characteristics previously demonstrated for PAH and phenol red transport by renal tubules, namely, a well-defined maximal rate, dependence upon Received for publication May 27, 1954. 1 Supported by a grant from the Rockefeller Foundation. aerobic phosphorylation as an energy source, and competitive inhibition when two or more of the tran sported substances are simultaneously present in plasma. METHODS All studies were made in vivo on Louisiana bullfrogs which ranged in weight from 300-500 gm. Exogenous creatinine clearances were determined to measure the rate of glomerular filtration (6). Urine was collected in a balloon which was attached in turn to a soft rubber indwelling cathether secured by a purse-string ligature around the anus. Fecal contamination was avoided by depriving the animals of food for a week or so prior to the experiment. The frogs were maintained individually in pans containing I$ in. of water, and care was taken to keep environmental conditions constant during urine …