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- W1970876926 abstract "Stimulation of Swiss 3T3 fibroblasts with platelet-derived growth factor (PDGF) results in a transient increase in intracellular free Ca2+ concentration ([Ca2+]i) and a phospholipase A2 (PLA2)-dependent release of arachidonic acid (AA) of 500% over control values. In the absence of extracellular Ca2+, both the PDGF-induced transient increase in [Ca2+]i and AA release were markedly reduced. Buffering the increase in [Ca2+]i with EGTA, introduced into the cells in the form of EGTA acetoxymethylester (AM), abolished the PDGF-induced transient increase in [Ca2+]i, but potentiated the AA release by at least 2-fold compared to cells without EGTA. The EGTA potentiated PDGF-induced AA release was sensitive to extracellular Ca2+ and inhibited to various degrees by both receptor-mediated as well as voltage-operated Ca2+ channel blockers, suggesting that the release of AA may be tightly coupled to the influx of Ca2+. Activation of protein kinase C (PKC) by the phorbol ester, phorbol 12-myristate 13-acetate (TPA) had little effect in promoting AA release by itself. Down-regulation of PKC in Swiss 3T3 fibroblasts by chronic stimulation with 300 nM TPA for 24 h, markedly inhibited the PDGF-stimulated AA release in both the EGTA-loaded and control cells. In conditions where PDGF-induced AA release was inhibited or potentiated, the production of inositol phosphates was unaffected. Thus, PDGF-induced PLA2 dependent AA release in Swiss 3T3 fibroblast is regulated by both PKC-dependent and -independent mechanisms, and is activated by high concentrations of free Ca2+ in the microenvironment beneath the plasma membrane during Ca2+ influx via plasma-membrane Ca2+ channels, despite buffering by EGTA of [Ca2+]i in the bulk cytoplasm of the cell." @default.
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- W1970876926 date "1993-10-01" @default.
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- W1970876926 title "Mechanisms of platelet-derived growth factor-induced arachidonic acid release in Swiss 3T3 fibroblasts: the role of a localized increase in free Ca2+ concentration beneath the plasma membrane and the activation of protein kinase C" @default.
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- W1970876926 doi "https://doi.org/10.1016/0167-4889(93)90074-y" @default.
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