Selective inhibition of urea transport by oxidizing agents - Evidence for a site of inhibition beyond the generation of cyclic AMP

Urea and water transport across the toad bladder epithelial cell appears to take place through independent vasopressin-stimulated pathways. Agents such as chromate, for example, when added to the luminal bathing medium, inhibit urea transport without inhibiting osmotic water flow, providing evidence for such independent pathways. In the present study, selective inhibition of urea transport is shown for permanganate and methylene blue, which, like chromate, are oxidizing agents. Permanganate inhibits urea transport irreversibly, while methylene blue acts reversibly. Not all oxidizing agents are inhibitory; perchlorate, peroxide and ferricyanide have no effect on urea transport or water flow. Permanganate and chromate both act at a point beyond the generation of cyclic AMP, since they continue to inhibit urea transport in bladders treated with exogenous cyclic AMP, 8-bromoadenosine 3′,5′-cyclic monophosphate, and a combination of cyclic AMP and theophylline. These findings suggest that selective inhibition of urea transport can be brought about by oxidation of one or more components in its transport pathway, and that, in the case of chromate and permanganate, these components may be in the luminal membrane itself.