[Pharmacologic modifications of renal tubular transport]

Possible mechanisms of transport of substances across renal tubular walls and of drug actions influencing these transports are discussed. The precise mechanisms of action of the majority of compounds which enhance or depress transtubular transports is still unknown. Certain inhibitors of transtubular transports may be competitors of the transported substances for tubular membrane carriers. Examples of changes in transtubular transports induced by drugs are reviewed. In the rat, the combined natriuretic and diuretic effects of furosemide and of compensatory adaptation, i.e. removal of the contralateral kidneys a few hours before the experiments, appear to be hyperadditive. The natriuretic and diuretic effects of acetazolamide are similarly enhanced under the conditions of compensatory adaptation. The data suggest that the natriuretic and diuretic effects of compensatory adaptation, on the one hand, and the diuretic agents, on the other hand, are due to different primary effects on the tubules. Bidirectional transports of uric acid across the walls of proximal convoluted tubules have been demonstrated in all species of animals investigated by micropuncture, microperfusion and microinjection. No net movements of uric acid occur across the wall of distal convoluted tubules. In species and under conditions of net reabsorption of uric acid by the whole kidney, the sum of the bidirectional transports across the walls of proximal convoluted tubules always results in pronounced net reabsorption. In species and races of animals characterized by overall tubular secretion of uric acid, the predominant movement in proximal convoluted tubules also tends to be net reabsorption, while the net secretion providing the amounts of uric acid, above the amounts filtered, appearing in the final urine, appears to occur in the straight parts of the proximal tubules. Possible mechanisms of action and micropuncture observations on the sites of actions of probenecid and of pyrazinolic acid, two agents which influence transtubular transports of uric acid, are discussed. The conclusion is reached that agents influencing transtubular uric acid transports probably always act on reabsorptive as well as on secretory transports and that the net result of their action on uric acid excretion may, therefore, vary in different species and under different experimental conditions. Enhancement of the urinary excretion of salicyclic acid by infusion of bicarbonate is a well-known fact. Recent micropuncture experiments indicate that this effect is probably due to either enhanced secretion or depressed reabsorption of salicylates in proximal convoluted tubules rather than on any changes of the rate of transtubular salicylate transports in lower segments of the nephron.