Protein kinase C activating phorbolesters enhance the cyclic AMP response to parathyroid hormone, forskolin and choleratoxin in mouse calvarial bones and rat osteosarcoma cells.
The protein kinase C-(PKC) activating phorbol esters 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nmol/l) and phorbol 12,13-dibutyrate (PDBU; 100 nmol/l) enhanced basal cyclin AMP accumulation in cultured neonatal mouse calvaria. The cyclic AMP response to parathyroid hormone (PTH; 10 nmol/l) and the adenylate cyclase activators forskolin (1-3 mumol/l) and choleratoxin (0.1 mumg/ml) was potentiated in a more than additive manner by TPA and PDBU. In contrast, phorbol 13-monoacetate (phorb-13; 100 nmol/l), a related compound but inactive on PKC, had no effect on basal or stimulated cyclic AMP accumulation. In the presence of indomethacin (1 mumol/l), TPA and PDBU had no effect on cyclic AMP accumulation in calvarial bones per se, but were still able to cause a significant enhancement of the response to PTH, forskolin and choleratoxin. PTH-, forskolin- and choleratoxin-stimulated cyclic AMP accumulation in rat osteosarcoma cells UMR 106-01 was synergistically potentiated by TPA and PDBU, but not by phorb.-13. These data indicate that PKC enhances cyclic AMP formation and that the level of interaction may be at, or distal to, adenylate cyclase.
Ransjö
M
M
Department of Oral Pathology, University of Umeå, Sweden.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002417:Cattle; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D010703:Phorbol Esters; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D002772:Cholera Toxin; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate