CAPK MEDIATES PLACENTAL RENIN SECRETION STIMULATED BY BETA-ADRENOCEPTOR ACTIVATION

Previous studies have indicated that activation of placental beta-adre noceptors stimulates renin secretion, whereas basal secretion is extre mely low. This response is potentiated by inhibition of types III and IV phosphodiesterases, implicating a role for adenosine 3',5'-cyclic m onophosphate (cAMP). Described are experiments aimed at defining the r egulatory influence of cAMP and cAMP-dependent protein kinase (cAPK) i sotypes in renin secretion. Human placental explants were cultured wit h dobutamine, a beta(1)-agonist, and cAPK activity, renin, and cAMP co ncentrations were determined. After 48 h of incubation, media concentr ations of renin and cAMP increased and were positively correlated. Tis sue cAPK activity was positively correlated with renin secretion assoc iated with dobutamine. Renin secretion was measured in response to sub stituted 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 threef old 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 place ntal renin secretion associated with beta-adrenoceptor activation is c orrelated with cAMP generation and mediated predominantly by the type II isoform of cAPK.