title: Effect of carbenoxolone on glucocorticoid metabolism and Na transport in toad bladder.
abstract: In humans, diminished 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) enzyme activity has been associated with sodium retention and hypertension. These studies show that the toad bladder, another target tissue epithelium displaying steroid-induced sodium transport, possesses the enzyme 11 beta-OHSD. The toad urinary bladder rapidly transformed corticosterone (3 x 10(-8) M) (50% by 10 min and 90% by 180 min) with 11-dehydrocorticosterone being the major metabolite. The 11-dehydrocorticosterone produced reached an apparent plateau when the tissue incubations were repeated with higher concentrations of corticosterone (10(-7) and 10(-6) M). Carbenoxolone sodium (2.5 x 10(-5) M), a water soluble derivative of glycyrrhetinic acid, markedly inhibited the metabolism of corticosterone (3 x 10(-8) M) to 11-dehydrocorticosterone similar to previous observations in the mammalian kidney. Carbenoxolone sodium (2.5 x 10(-5) M) did not significantly affect short-circuit current (SCC) in toad bladders when added to either the serosal or mucosal bath. However, when carbenoxolone sodium was added to the mucosal bath and 60 min later corticosterone 10(-6) M was placed in the serosal bath, bladders generated a SCC 2.07 +/- 0.17 (mean +/- SE) times above base line at 360 min compared with 1.48 +/- 0.11 in bladders exposed to corticosterone alone (P less than 0.02). In parallel experiments, carbenoxolone sodium in the mucosal bath enhanced the rise in SCC induced by cortisol 10(-6) M; 1.66 +/- 0.16 times above base line at 360 min compared with 1.07 +/- 0.14 with cortisol alone (P less than 0.02). We conclude that the toad bladder contains 11 beta-OHSD and inhibition of this enzyme with carbenoxolone sodium is associated with amplification of glucocorticoid-induced transepithelial sodium transport in this tissue. However, since the quantity of 11-dehydro-product produced appears to be limited, other factors in addition to inhibition of 11 beta-OHSD may play a role in this amplification of sodium transport.
authors.affiliation: Division of Pediatric Nephrology, Rhode Island Hospital, Providence 02902.
authors.forename: A S
authors.initials: AS
authors.lastname: Brem
authors.forename: K L
authors.initials: KL
authors.lastname: Matheson
authors.forename: T
authors.initials: T
authors.lastname: Conca
authors.forename: D J
authors.initials: DJ
authors.lastname: Morris
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002024:Bufo marinus; D002229:Carbenoxolone / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism*; D006034:Glycyrrhetinic Acid; D066298:In Vitro Techniques; D007700:Kinetics; D012964:Sodium / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D012964:Sodium; D002229:Carbenoxolone; D006034:Glycyrrhetinic Acid; D003345:Corticosterone