Early alterations in cytosolic free Ca2+ concentration (Ca2+(i)) (occurring within seconds to minutes) following platelet-derived growth factor (PDGF) stimulation were demonstrated to be required, in both BALB/c3T3 fibroblasts and vascular smooth muscle cells, for subsequent DNA synthesis by introduction of Ca2+-antagonists at different times in relation to growth factor stimulation. Blockade of PDGF-stimulated increases in Ca2+(i) correlated with inhibition of PDGF-stimulated DNA synthesis in both systems, although the mechanism of increased Ca2+(i) is different in the two cell types. In vascular smooth muscle cells, voltage-sensitive Ca2+-channel antagonists, TPA, and pertussis toxin inhibited both PDGF-induced increases in Ca2+(i) and DNA synthesis when added immediately before PDGF, but did not do so when added for the same time period 4 hr after PDGF. Similarly, pretreatment of fibroblasts with TMB-8 inhibited PDGF-induced alterations in Ca2+(i) and DNA synthesis, but had no effect on DNA synthesis when added after PDGF exposure. These findings demonstrate for the first time that early increases in Ca2+(i) stimulated by PDGF play a critical role in PDGF-stimulated mitogenesis.
|Original language||English (US)|
|Number of pages||10|
|Journal||Research Communications in Chemical Pathology and Pharmacology|
|State||Published - 1991|