EFFECTS OF CORTICOID AGONISTS AND ANTAGONISTS ON APICAL NA-BLADDER( PERMEABILITY OF TOAD URINARY)

Effects of RU-28362 (glucocorticoid agonist), RU-38486 (glucocorticoid antagonist), and RU-26752 (mineralocorticoid antagonist) on the apica l Na+ permeability of toad bladder were measured and correlated with o ccupancies of cytosolic type I (mineralocorticoid) and type II (glucoc orticoid) receptors. Effects of the above steroids were measured in wh ole bladders, plasma membrane vesicles, and RNA-injected Xenopus oocyt es. RU-38486 was found to fully displace aldosterone from type II rece ptors without affecting type I occupancy. Under these conditions, RU-3 8486 inhibited similar to 35% of the effect of aldosterone measured in the whole tissue and isolated membranes. Unexpectedly, oocytes inject ed with RNA from tissue stimulated with aldosterone plus RU-38486 expr essed channel activity that was much higher than the sum of activities induced by either steroid alone. RU-28362 and RU-26752 at concentrati ons sufficient to fully occupy both receptors had only partial agonist ic and antagonistic effects, respectively. The results suggest that at least one-third of the natriferic action of aldosterone measured in t he amphibian urinary bladder is mediated by the glucocorticoid recepto r. However, some of the effects observed cannot be accounted for by a simple receptor occupancy-response scheme.