Aldosterone stimulates active Na+ transport in rabbit urinary bladder by both genomic and non-genomic processes.
The ability of aldosterone to stimulate Na+ transport in a range of epithelial tissues has been known for many years. Early work suggested that aldosterone had a delayed action operating by transcriptional up-regulation of proteins such as the epithelial Na+ channel. However more recent data has suggested that the hormone has a short-term non-genomic action. In this paper we investigate short and long-term actions of aldosterone on Na+ transport in the rabbit urinary bladder. We have shown that aldosterone stimulates epithelial Na+ channel activity, as measured by the amiloride-sensitive short-circuit current over a 3.75 h period and that this action is potentiated by cAMP. Using reverse transcriptase-polymerase chain reaction we have shown that aldosterone and forskolin in combination up-regulate mRNA synthesis for the beta- and gamma-subunits of the epithelial Na+ channel. Using Western blotting we have shown in the case of the beta-subunit that a corresponding increase in channel protein occurs. We have also demonstrated that aldosterone in the presence of inhibitors of phosphodiesterase can stimulate the short-circuit current across rabbit bladder epithelium over a 20 min period. An explanation for the synergistic interaction between aldosterone and cAMP is provided. We have shown that aldosterone can increase cAMP levels within urothelial cells over a 4 min period. We propose that this represents a non-genomic action of the steroid hormone.
Burton
Timothy J
TJ
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.
Cooper
Dermot M F
DM
Dunning-Davies
Bryony
B
Mansour
Dina
D
Masada
Nanako
N
Ferguson
Douglas R
DR
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000235:genetics; D053503:Epithelial Sodium Channels; D005260:Female; D023281:Genomics; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism*; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D015222:Sodium Channels; D000450:Aldosterone; D004247:DNA; D012964:Sodium; D000242:Cyclic AMP