Involvement of Ca(2+)-calmodulin in platelet-derived growth factor-, fibroblast growth factor-, and insulin-induced ornithine decarboxylase in NIH-3T3 cells.
Ornithine decarboxylase (ODC) was induced by platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and insulin at doses ranging from 0.125 to 0.5 U/mL, 25 to 500 ng/mL, and 10(-8) to 10(-7) mol/L, respectively, in NIH-3T3 cells. The induction of ODC reached a plateau approximately 4 to 6 hours after addition of each mitogen. PDGF exerted a synergistic action with 10(-7) mol/L insulin until the concentration of PDGF reached 0.5 U/mL and exerted an additive action at concentrations greater than 0.5 U/mL. FGF also accelerated ODC induction by insulin (10(-7) mol/L) synergistically when it was added at doses up to 500 ng/mL. PDGF added to the intact monolayer cells caused a spike-and-plateau increase in cytosolic Ca2+ concentration ([Ca2+]i); the spike was independent of extracellular Ca2+, whereas the plateau formation was dependent on extracellular Ca2+. On the other hand, FGF caused a plateau-like increase in [Ca2+]i, exclusively dependent on extracellular Ca2+. Insulin did not affect [Ca2+]i in NIH-3T3 cells. Trifluoperazine (15 to 30 mumol/L) inhibited the induction of ODC by PDGF and FGF, but did not inhibit the effect of insulin to induce ODC. N-(6-aminohexyl)-5-chloro-1-Naphthalenesulfonamide ([W-7] 30 to 40 mumol/L) showed a more profound suppressive effect on ODC induced by PDGF and FGF than N-(6-aminohexyl)-naphthalenesulfonamide (W-5) did. There was no difference between the effects of W-7 and W-5 on ODC induction by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Katori
T
T
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Yasuda
H
H
Fukuda
H
H
Kimura
S
S
D016475:3T3 Cells / Q000737:chemistry / Q000201:enzymology*; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D002147:Calmodulin / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D013449:Sulfonamides; D016222:Fibroblast Growth Factor 2; D014268:Trifluoperazine; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D009955:Ornithine Decarboxylase; D002118:Calcium