PMID- 6193130 OWN - NLM STAT- MEDLINE DCOM- 19831028 LR - 20151119 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 116 IP - 3 DP - 1983 Sep TI - Mitogenic effect of prostaglandin E1 in Swiss 3T3 cells: role of cyclic AMP. PG - 379-84 AB - Addition of prostaglandin E1 (PGE1) to quiescent cultures of Swiss 3T3 cells rapidly elevates the intracellular levels of cAMP and increases the activity of adenylate cyclase in particulate fractions of these cells. In the presence of insulin, PGE1 stimulates the reinitiation of DNA synthesis. Both effects (increase in cellular cAMP and stimulation of DNA synthesis) are markedly potentiated by 1-methyl-3-isobutyl xanthine (IBMX) or by 4-(3-butoxy-4 methoxy benzyl)-2-imidazolidine (Ro 20-1724), both of which are potent inhibitors of cyclic nucleotide phosphodiesterase activity. In the presence of 50 microM IBMX, PGE1 caused a dose-dependent increase in cAMP levels and in [3H]thymidine incorporation into acid-insoluble material at concentrations (5-50 ng/ml) that are orders of magnitude lower than those used in previous studies (50 micrograms/ml) to demonstrate growth-inhibitory effects. Thus, the inhibitory effects produced by adding high concentrations of PGE1 on the initiation of DNA synthesis in Swiss 3T3 cells are not mediated by cAMP and should be regarded as nonspecific. In contrast, the mitogenic activity of PGE1 parallels its ability to increase the intracellular levels of cAMP. The findings support the proposition that a sustained increase in the level of this cyclic nucleotide acts as a mitogenic signal for confluent and quiescent Swiss 3T3 cells. FAU - Rozengurt, E AU - Rozengurt E FAU - Collins, M K AU - Collins MK FAU - Keehan, M AU - Keehan M LA - eng PT - Journal Article PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Insulin) RN - 0 (Mitogens) RN - 0 (Prostaglandins E) RN - 9007-49-2 (DNA) RN - E0399OZS9N (Cyclic AMP) RN - EC 4.6.1.1 (Adenylyl Cyclases) RN - F5TD010360 (Alprostadil) RN - K7Q1JQR04M (Dinoprostone) RN - TBT296U68M (1-Methyl-3-isobutylxanthine) SB - IM MH - 1-Methyl-3-isobutylxanthine/pharmacology MH - Adenylyl Cyclases/metabolism MH - Alprostadil MH - Animals MH - Cell Line MH - Cells, Cultured MH - Cyclic AMP/*metabolism MH - DNA/biosynthesis MH - Dinoprostone MH - Dose-Response Relationship, Drug MH - Drug Interactions MH - Insulin/pharmacology MH - Mice MH - Mice, Inbred Strains MH - Mitogens/*pharmacology MH - Prostaglandins E/*pharmacology EDAT- 1983/09/01 00:00 MHDA- 1983/09/01 00:01 CRDT- 1983/09/01 00:00 PHST- 1983/09/01 00:00 [pubmed] PHST- 1983/09/01 00:01 [medline] PHST- 1983/09/01 00:00 [entrez] AID - 10.1002/jcp.1041160316 [doi] PST - ppublish SO - J Cell Physiol. 1983 Sep;116(3):379-84. doi: 10.1002/jcp.1041160316.