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Adenosine 3',5'-Monophosphate (cAMP)-Binding Protein and cAMP-Dependent Protein Kinase in Human Placenta^*

John J. Moore, Jeffrey V. Baker and Jeffrey A. Whitsett

Children's Hospital Research Foundation, Newborn Division, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267

Address requests for reprints to John J. Moore, Jr., M.D., Department of Pediatrics, Metropolitan General Hospital, 3395 Scranton Road, Cleveland, Ohio 44109.

cAMP modulates estrogen, hCG, and lactate syntheses by human placenta. cAMP presumably exerts its major intracellular effect by binding to cAMP-dependent protein kinase (cAMP-PK), which, in turn, phosphorylates regulatory proteins within the target cell. cAMP binding and cAMP-PK have not been previously identified in placenta. [³H]cAMP binding to crude cytosol fractions of term placenta was rapid, saturable, and reversible. Scatchard analyses of saturation experiments of [³H]cAMP binding to placental cytosol were linear (K_a = 1.13 ± 0.11 x 10^–8 M; n = 5). The binding capacity was 1.27 ± 0.18 pmol/mg protein. Competition for the [³H]cAMP-binding site followed the potency order cAMP >> cGMP >> (Bu)₂cAMP, analogous to cAMP binding to cAMP-PK in other tissues. ADP, ATP, and adenosine did not compete for the [³H]cAMP-binding site. cAMP significantly enhanced phosphorylation of histone protein by placental cytosol (activity ratio, 0.57 ± 0.04; P < 0.01). Two peaks of [³H]cAMP binding and coincident cAMPPK activity were identified by DEAE-cellulose column chromatography of placental cytosol corresponding to classical type I and type II cAMP-PK. While the majority of the cAMP-PK was found in placental cytosol, cAMP-PK was also demonstrated in crude microsomal and microvillous brush border membranes of human placenta after solubilization with Triton X-100 (P < 0.05). Regulation of placental function by catecholamines and other hormones known to mediate cAMP levels may be accomplished through the phosphorylation of cellular proteins by cAMP-dependent protein kinases. (J Clin Endocrinol Metab 56: 1035, 1983)

^* This work was supported in part by NICHHD Grants 11725 and 07200, the Department of Health and Human Service, Maternal and Child Health Training Grant 000174 (to J.J.M.), and the Children's Hospital Research Foundation.

Supported by Research Career Development Award HL-01024.

Received September 1, 1982.