Inhibition of receptor-mediated stimulation of cyclic AMP accumulation in neuroblastoma-hybrid NCB-20 cells by a phorbol ester.
Activation of protein kinase C by phorbol esters such as phorbol 12-myristate 13-acetate (PMA), modulates responsiveness of the cyclase system in many cell types. In the neuroblastoma-hybrid cell line NCB-20, PMA causes a reduction in receptor-mediated accumulation of cyclic AMP. The reduction in receptor responses by PMA occurs within 3 min and is still apparent at 40 min. This occurs in a concentration-dependent manner with an EC50 for PMA of approx. 30 nM. Accumulations of cyclic AMP that are elicited by prostaglandin E2, vasoactive intestinal peptide or 2-chloroadenosine are decreased in the presence of PMA. Accumulations of cyclic AMP that are elicited by forskolin in the absence of a receptor agonist are unaffected by the presence of PMA. Inhibition of cyclic AMP generation by dopamine is not diminished by PMA suggesting the receptor input through the inhibitory Ni-guanyl nucleotide binding protein is still functional after PMA treatment. The generalized inhibition of receptor-mediated responses by PMA could be due to a protein kinase C-mediated phosphorylation of the stimulatory Ns-guanyl nucleotide binding protein, but other mechanisms are possible.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D004298:Dopamine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006822:Hybrid Cells; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D010766:Phosphorylation; D011458:Prostaglandins E / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D005576:Colforsin; D000242:Cyclic AMP; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine