Steps in p-aminohippurate transport by kidney slices

Abstract

The existence of two intracellular fractions of PAH was demonstrated in renal cortical slices of the rabbit on incubation with C14-labeled PAH. One of these fractions is rapidly diffusible and rapidly equilibrates with extracellular PAH. The other fraction, in contrast, diffuses and equilibrates slowly; it is responsible for the high slice to medium concentration ratio of PAH. On the basis of these results a model of the PAH transport system in slices is proposed. This consists of step I, the diffusion of PAH from the medium into the extracellular space in the tissue; there follows step II, a facilitated diffusion step at the peritubular cell membrane; within the cell step III builds up a high tissue concentration of PAH; finally step IV transfers PAH across the luminal border of the cell into the tubular lumen from which it may diffuse back into the medium. Experiments were designed in which each of these steps could be measured individually and their rate constants determined. Alteration of the value of these rate constants by specific drugs localizes the action of such compounds at the peritubular cell membrane (Benemid, 9-alphafluorohydrocortisone) or at the level of both steps II and III in the case of DNP, octanoate and Diodrast. An explanation is also offered for the effect of cold on PAH influx and efflux. It can be calculated that the contribution of step IV to the turnover of PAH in slices is not quantitatively significant.