Cyclic AMP inhibits mitogen-induced DNA synthesis in hamster fibroblasts, regardless of the signalling pathway involved.
Mitogen-induced initiation of DNA synthesis in quiescent Chinese hamster lung fibroblasts (CCL39) is strongly inhibited by 8-Br cAMP and cAMP-evaluating agents (prostaglandin E1, cholera toxin, isobutylmethylxanthine). This inhibition is reversible and occurs very early in G0/G1. As exponential growth is much less affected by increased cAMP, we propose that cAMP inhibits an early signal essential for the exit from G0. CCL39 cells can be stimulated by alpha-thrombin, which activates phosphoinositide (PI) breakdown, as well as by mitogens (FGF or FGF + serotonin) which do not involve the PI pathway. Here we show that the action of both classes of mitogens is likewise inhibited by cAMP. Therefore, although PI breakdown is inhibited by cAMP in CCL39 cells, this effect cannot entirely account for th antimitogenic activity of cAMP. Other early steps of the mitogenic response must be also affected.
Magnaldo
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Centre de Biochimie du CNRS, Faculté des Sciences, Parc Valrose, Université de Nice, France.
Pouysségur
Paris
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D007399:Interphase; D008934:Mitogens / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology
D008934:Mitogens; D010716:Phosphatidylinositols; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; D005346:Fibroblast Growth Factors; D004247:DNA; D002772:Cholera Toxin; D000242:Cyclic AMP; D013917:Thrombin; D000527:Alprostadil; D015056:1-Methyl-3-isobutylxanthine