A transient rise in cytosolic calcium follows stimulation of quiescent cells with growth factors and is inhibitable with phorbol myristate acetate.

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Abstract
Aequorin was used as an indicator for the intracellular free Ca++ concentration ([Ca++]i) of Swiss 3T3 fibroblast. Estimated [Ca++]i of serum-deprived, subconfluent fibroblasts was 89 (.+-. 20) nM, almost 2-fold higher than that of subconfluent cells growing in serum, whose [Ca++]i was 50 (.+-. 19) nM. Serum, partially purified platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) stimulated DNA synthesis by the serum-deprived cells, whereas epidermal growth factor (EGF) did not. Serum immediately and transiently elevated the [Ca++]i of serum-deprived cells, which reached a maximal value of 5.3 .mu.M at 18 s poststimulation but returned to near prestimulatory levels within 3 min. No further changes in [Ca++]i were observed during 12 subsequent h of continuous recording. PDGF produced a peak rise in [Ca++]i to .apprx. 1.4 .mu.M at 115 s after stimulation, and FGF to .apprx. 1.2 .mu.M at 135 s after stimulation. EGF caused no change in [Ca++]i. The primary source of Ca for these transients was intracellular, since the magnitude of the serum-induced rise in [Ca++]i was reduced by only 30% in the absence of exogenous Ca. Phorbol 12-myristate 13-acetate (PMA) had no effect on resting [Ca++]i. When quiescent cells were treated for 30 min with 100 nM PMA, serum-induced rises in [Ca++]i were reduced by 7-fold. PMA did not inhibit growth factor-induced DNA synthesis and was by itself partially mitogenic. If Ca is involved as a cytoplasmic signal for mitogenic activation of quiescent fibroblasts, its action is early, transient, and can be partially substituted for by PMA. Activated protein kinase C may regulate growth factor-induced increases in [Ca++]i.