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- W2054348666 abstract "Tumor necrosis factor (TNF) actions in target tissues are mediated by various signalling pathways. The effect of TNF to stimulate resorption in fetal rat limb bones is not inhibited by indomethacin. The current studies were designed to assess the role of cyclic AMP (cAMP) and calcium as second messengers in this prostaglandin-independent action of TNF on bone resorption. TNF alone failed to increase cyclic AMP in fetal rat limb bones after either brief (15 min) or long-term (72 h) treatment. TNF-stimulated resorption in fetal rat limb bones was enhanced by the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX). In short term incubations, the combination of TNF + IBMX did not elicit increases in cAMP in the limb bones. In 72 h cultures, addition of IBMX revealed a dose-dependent effect of TNF to increase cAMP. TNF produced a significant increase in inositol phosphate turnover in limb bones, with a greater response at 5 min than at 1 or 20 min. The calcium channel blocker nitrendipine inhibited TNF-stimulated resorption in the fetal rat limb bones. TNF-stimulated resorption was attenuated by pretreatment with pertussis toxin (PTx). PTx did not inhibit the effect of TNF to increase inositol phosphate turnover. TNF did not increase cAMP, intracellular calcium, or inositol phosphates in the UMR-106 cells. The data suggest the following: (a) cyclic mucleotides may play a role in TNF-stimulated resorption, although an increase in cAMP is not a direct rapid effect of TNF per se; (b) inositol phosphates could also play a signalling role in the action of TNF; (c) a pertussis toxin-sensitive step is required for TNF action on bone resorption." @default.
- W2054348666 created "2016-06-24" @default.
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- W2054348666 date "1993-11-01" @default.
- W2054348666 modified "2023-09-24" @default.
- W2054348666 title "Evaluation of the role of second messenger systems in tumor necrosis factor-stimulated resorption of fetal rat limb bones" @default.
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- W2054348666 doi "https://doi.org/10.1016/8756-3282(93)90317-4" @default.
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