On the role of cyclic AMP in the cytotoxic effect of fluoride.
The possible role of adenosine 3',5'-monophosphate (cAMP) in the cytotoxic effect of fluoride was investigated in fluoride sensitive mouse fibroblasts (LS) and a subline of LS resistant to 6 mM fluoride (FR6). In both cell lines, growth was inhibited by dibutyryl-cAMP, prostaglandin (PG)E2 and theophylline, FR6 being somewhat more sensitive to these agents than LS. FR6 had lower basal cAMP levels in the intact cells and lower basal adenylate cyclase activity in the homogenate preparation than LS, but the percentual response of intact cells or adenylate cyclase preparations to PGE1 or PGE2 was about the same in the two cell lines, and the sensitivity of the adenylate cyclase to fluoride was similar. No measurable increase in cAMP content was found in either LS or FR6 after exposure of the intact cells to various concentrations of fluoride for various times. The present results indicate that the development of fluoride resistance in these cells is not due to decreased sensitivity to cAMP, and probably not due to altered cAMP-formation in response to fluoride. The growth inhibitory and cytotoxic effects of fluoride in LS cells is probably not mediated through cAMP.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D004837:Epinephrine / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology*; D051379:Mice; D011458:Prostaglandins E / Q000494:pharmacology; D014176:Protein Biosynthesis; D013806:Theophylline / Q000494:pharmacology
D003470:Culture Media; D011458:Prostaglandins E; D003994:Bucladesine; D004247:DNA; D013806:Theophylline; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005459:Fluorides; D004837:Epinephrine