THE INHIBITION OF DNA-SYNTHESIS BY PROSTAGLANDIN E-2 IN HUMAN GINGIVAL FIBROBLASTS IS INDEPENDENT OF THE CYCLIC AMP-PROTEIN KINASE A SIGNAL-TRANSDUCTION PATHWAY

In this study we attempted to clarify the mechanism of the inhibitory effects of PGE(2) on DNA synthesis in Gin-1 (fibroblasts derived from healthy human gingiva) from the aspect of the cyclic AMP-dependent pro tein kinase signal transduction pathway. PGE(2) upregulated intracellu lar cyclic AMP accumulation and inhibited DNA synthesis in Gin-1 in a dose-dependent manner. When the PGE(2)-induced intracellular cyclic AM P accumulation was further enhanced by treatment with the cyclic AMP-p hosphodiesterase inhibitor, IBMX, the inhibitory effect of PGE(2) on D NA synthesis was also enhanced. Furthermore, when we examined the effe cts of forskolin, an activator of cyclic AMP production, on intracellu lar cyclic AMP accumulation and DNA synthesis, similar results were ob tained. However, inhibitors of cyclic AMP-dependent protein kinase (pr otein kinase A) such as HA1004 did not diminish the inhibitory effect of PGE(2) on DNA synthesis in Gin-1. These results suggest that in Gin -1, PGE(2)-induced cyclic AMP accumulation may not lead to the activat ion of protein kinase A or protein kinase A activity may not relate di rectly to the growth inhibitory effect of PGE(2), and that PGE(2) does not inhibit DNA synthesis through the cyclic AMP-protein kinase A sig nal transduction pathway in Gin-1.