Effects of corticoid agonists and antagonists on apical Na+ permeability of toad urinary bladder.
Effects of RU-28362 (glucocorticoid agonist), RU-38486 (glucocorticoid antagonist), and RU-26752 (mineralocorticoid antagonist) on the apical Na+ permeability of toad bladder were measured and correlated with occupancies of cytosolic type I (mineralocorticoid) and type II (glucocorticoid) receptors. Effects of the above steroids were measured in whole bladders, plasma membrane vesicles, and RNA-injected Xenopus oocytes. RU-38486 was found to fully displace aldosterone from type II receptors without affecting type I occupancy. Under these conditions, RU-38486 inhibited approximately 35% of the effect of aldosterone measured in the whole tissue and isolated membranes. Unexpectedly, oocytes injected with RNA from tissue stimulated with aldosterone plus RU-38486 expressed channel activity that was much higher than the sum of activities induced by either steroid alone. RU-28362 and RU-26752 at concentrations sufficient to fully occupy both receptors had only partial agonistic and antagonistic effects, respectively. The results suggest that at least one-third of the natriferic action of aldosterone measured in the amphibian urinary bladder is mediated by the glucocorticoid receptor. However, some of the effects observed cannot be accounted for by a simple receptor occupancy-response scheme.
Garty
H
H
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Peterson-Yantorno
K
K
Asher
C
C
Civian
M M
MM
D000305:Adrenal Cortex Hormones / Q000037:antagonists & inhibitors* / Q000502:physiology*; D000450:Aldosterone / Q000494:pharmacology; D000732:Androstanols / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002024:Bufo marinus; D002463:Cell Membrane Permeability; D007267:Injections; D015735:Mifepristone / Q000378:metabolism / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D012313:RNA / Q000494:pharmacology; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D001743:Urinary Bladder / Q000378:metabolism*; D014981:Xenopus
D000305:Adrenal Cortex Hormones; D000732:Androstanols; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D015735:Mifepristone; D000450:Aldosterone; D012313:RNA; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D012964:Sodium