The mechanism of the excretion of ammonia in the dog.

The excretion of ammonia is dependent upon several factors: the amount and duration of acid intake, presumably affecting variations in intracellular enzyme activity (1-3), the availability of precursors from which ammonia can be formed (4-6), and the pH of the urine (7-9). With respect to the effect of urine pH, the excretion of ammonia resembles that of a number of organic bases, such as quinine (10), nicotine (11), procaine (12), Atabrine@ (13), and certain derivatives of 4-aminoquinoline (13), all of which appear in the urine at a rate inversely related to urine pH. The experiments to be reported were designed to reexamine this phenomenon and to compare ammonia excretion with that of selected organic bases in order to provide information concerning 1) the nature of the process by which ammonia enters the urine, 2) the production of ammonia by the cells of the renal tubules, 3) the mechanism of excretion of other weak electrolytes, the output of which is dependent upon urine pH, and 4) to yield an interpretation of the quantitative relations between ammonia excretion and urine pH. Since the factors which affect the transport of the organic bases are similar to those affecting the movement of ammonia into the urine, it was anticipated that the excretion of these bases might be used as a means of independently evaluating the factors affecting the transport of ammonia as contrasted with those affecting intracellular production. In acute experiments the clearance of quinine was found to serve this purpose since it was influenced by pH only and the excretion of ammonia by both urine pH and by circumstances which might be presumed to influence rate of production. However, it was not possible to extend these principles to chronic experiments since the absolute level of quinine clearance varied at the same pH in different experiments in an unpredictable fashion. The results of the studies are in accord with the view (9, 14) that ammonia formed in the tubule cell enters the urine almost exclusively in the uncharged state, i.e., as the free base NH3, and accumulates as NH,+. The extent of accumulation is probably limited in the acid range of urine pH by the rate of ammonia production. At higher pH's, production of ammonia is non-limiting and the rate of excretion is dependent upon equilibration of ammonia in the tubule urine with that in tubule cell. Similar considerations also apply to the urinary loss of other weak electrolytes whose excretion is modified by changes in urine pH except insofar as rate of diffusion, rather than rate of production, is presumably the limiting factor in the acid range. The data have further been interpreted to indicate that final changes in urine volume are effected by abstraction of water in the tubule at a site beyond which final ammonia content is achieved.