Vasoactive intestinal peptide synergistically stimulates DNA synthesis in mouse 3T3 cells: role of cAMP, Ca2+, and protein kinase C.
Vasoactive intestinal peptide synergistically stimulated initiation of DNA synthesis in Swiss 3T3 cells. The peptide stimulated [3H]thymidine incorporation in the presence of insulin and either forskolin or an inhibitor of cAMP phosphodiesterase in a concentration-dependent manner. Half-maximal effect was obtained at 1 nM. At mitogenic concentrations, VIP stimulated a marked accumulation (eightfold) of cAMP. In contrast to other growth-promoting neuropeptides, VIP did not induce an increase in cytosolic free Ca2+ or an activation of protein kinase C. We conclude that neuropeptides can modulate long-term cell proliferation through multiple signaling pathways.
Zurier
R B
RB
Imperial Cancer Research Fund, London, United Kingdom.
Kozma
M
M
Sinnett-Smith
J
J
Rozengurt
E
E
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002453:Cell Cycle; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis*; D004357:Drug Synergism; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D007328:Insulin; D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D004247:DNA; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium