cAPK mediates placental renin secretion stimulated by beta-adrenoceptor activation.
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.
Downing
G J
GJ
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
Poisner
A M
AM
D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000032:analysis; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004280:Dobutamine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012083:Renin / Q000378:metabolism*
D007527:Isoenzymes; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D000242:Cyclic AMP; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D012083:Renin