Renal tubular transport: effect of 2,4-dinitrophenol and related compounds on phenol red transport in the isolated tubules of the flounder.

I N RECENT years clearance techniques have been developed which permit precise measurements of the rates at which some substances are transported from tubular lumen to peritubular capillaries (glucose, amino acids, ascorbic acid, etc.) and others from peritubular fluid to the lumina of the tubules (p-aminohippurate, diodrast, phenol red, etc.). Many of the tubular excretory and reabsorptive processes are characterized by the movement of a solute against a concentration gradient. Such active transport mechanisms obviously require expenditure of energy and, consequently, are inextricably linked with the metabolic activities of the cell. Relatively little is known concerning the biochemical events which underlie active transport mechanisms in the kidney. It has been proposed, on the basis of histochemical evidence and biochemical and physiological experiments with phloridzin (cf. I for review), that glucose transport involves the stepwise phosphorylation and dephosphorylation of glucose in the cells of the proximal convoluted tubule. In the cases of other active transport systems, such as those concerned with the tubular excretion of diodrast, p-aminohippurate, phenol red and penicillin, no obvious mechanism can be deduced from available biochemical information. However, it may be presumed that the transported substance undergoes a series of two or more reactions during its passage across the tubular epithelium. At least one of these reactions must involve the participation of an energy-donating system. The importance of energy-rich phosphate compounds in various biological syntheses, in muscle contraction (2), the transmission of the nerve impulse (3), etc., suggests that they may play a similarly important role in renal tubular processes. Recent observations on aerobic phosphorylation (4) appeared to offer an experimental approach whereby the participation of phosphate bond energy in cellular transport might be uncovered. Of particular importance to the present studies is the finding that 2 ,+dinitrophenol (DNP), in concentrations as low as 5 )( IO-~ M, is capable of interrupting the coupling of oxidation and phosphorylation in respiring, washed cell particle preparations of mammalian kidney, such as that