Rapid stimulation of cyclic AMP production by aldosterone in rat inner medullary collecting ducts.
Aldosterone stimulates sodium transport in the inner medullary collecting duct (IMCD) via the classic genomic pathway, but it is not known whether it also acts via a rapid, non-conventional pathway in this part of the nephron. The IMCD regulates the final sodium content of urine and expresses vasopressin receptors coupled to adenylate cyclase. The recently reported rapid, non-genomic actions of aldosterone have been associated mainly with an increase in intracellular Ca(2+); however, it has also been shown to stimulate camp generation. Thus the aim of this study was to determine whether aldosterone stimulates rapid generation of cAMP in isolated IMCD segments. IMCD segments were microdissected from Sprague-Dawley rat kidneys and incubated at 37 degrees C for 4 min with aldosterone (10(-12) to 10(-6) M), vasopressin (10(-12) to 10(-6) M), or a combination of hormones in the presence of a phosphodiesterase inhibitor. cAMP was measured by radioimmunoassay. While corticosterone and dexamethasone were ineffective, aldosterone stimulated a dose-dependent increase in cAMP within 4 min (P<0.05). This action of aldosterone was not inhibited by the MR antagonist spironolactone. Co-incubation of aldosterone with vasopressin resulted in a further increase in cAMP generation above that induced by the neurohypophysial hormone alone. Aldosterone-mediated cAMP generation was not inhibited by a vasopressin V(1) or V(2) receptor antagonist. These data support a novel and rapid, non-genomic effect of aldosterone in IMCD. Aldosterone does not apparently interact with the vasopressin receptor to stimulate cAMP generation.
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School of Biological Sciences, University of Manchester, UK.
Wargent
E T
ET
Ashton
N
N
Balment
R J
RJ
D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001127:Arginine Vasopressin; D000450:Aldosterone; D003907:Dexamethasone; D000242:Cyclic AMP; D003345:Corticosterone