AJP - Endocrinology and Metabolism, Vol 267, Issue 6 E954-E960, Copyright © 1994 by American Physiological Society
cAPK mediates placental renin secretion stimulated by beta-adrenoceptor activation
G. J. Downing and A. M. Poisner
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
Previous studies have indicated that activation of placental
beta-adrenoceptors stimulates renin secretion, whereas basal secretion is
extremely low. This response is potentiated by inhibition of types III and
IV phosphodiesterases, implicating a role for adenosine 3',5'-cyclic
monophosphate (cAMP). Described are experiments aimed at defining the
regulatory influence of cAMP and cAMP-dependent protein kinase (cAPK)
isotypes in renin secretion. Human placental explants were cultured with
dobutamine, a beta 1-agonist, and cAPK activity, renin, and cAMP
concentrations were determined. After 48 h of incubation, media
concentrations of renin and cAMP increased and were positively correlated.
Tissue cAPK activity was positively correlated with renin secretion
associated with dobutamine. Renin secretion was measured in response to
substituted cAMP analogues selective for a unique cAMP binding site (site A
or B) for cAPK regulatory subunits. A fivefold stimulation of renin
secretion by the type II site B activators occurred, whereas a threefold
increase was seen with a type I site B analogue. Site A-selective analogues
for cAPK types I and II produced no stimulation. Dobutamine-induced renin
secretion was attenuated by selective inhibitors of cAPK regulatory and
catalytic subunits. These findings indicate that placental renin secretion
associated with beta-adrenoceptor activation is correlated with cAMP
generation and mediated predominantly by the type II isoform of cAPK.
