Platelet-derived growth factor stimulates non-mitochondrial Ca2+ uptake and inhibits mitogen-induced Ca2+ signaling in Swiss 3T3 fibroblasts

G. Powis, M. J. Seewald, I. Sehgal, P. A. Iaizzo, R. A. Olsen

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9 Scopus citations

Abstract

Changes in intracellular free Ca2+ concentration ([Ca2+](i)) were used to study the interaction between mitogens in Swiss 3T3 fibroblasts. Platelet-derived growth factor (PDGF) produced an increase in [Ca2+](i) and markedly decreased the increases in [Ca2+](i) caused by subsequent addition of bradykinin and vasopressin. If the order of the additions was reversed the [Ca2+](i) response to PDGF was not inhibited by bradykinin or vasopressin. Inhibition of protein kinase C by staurosporine or chronic treatment of the cells with phorbol 12-myristate 13-acetate prevented the inhibitory effect of PDGF on the [Ca2+](i) response to vasopressin but not bradykinin. PDGF did not decrease the receptor binding of bradykinin and produced only a small decrease in the receptor binding of vasopressin. PDGF decreased the rise in [Ca2+](i) caused by the Ca2+ ionophores 4-bromo-A23187 and ionomycin and by a membrane perturbing ether lipid, 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine, both in the presence and absence of external Ca2+. There was no change in cell 45Ca2+ influx caused by PDGF, vasopressin, or bradykinin. 45Ca2+ efflux from cells exposed to PDGF and vasopressin mirrored the changes in [Ca2+](i) caused by the agents, that is, PDGF added after vasopressin produced a further increase in 45Ca2+ but vasopressin did not increase 45Ca2+ efflux after PDGF. PDGF but not vasopressin caused an increase in the uptake of 45Ca2+ into an inositol 1,4,5-trisphosphate-insensitive non-mitochondrial store in permeabilized cells. The results suggest that the decreased [Ca2+](i) response to mitogens after PDGF represents an action of PDGF at a point beyond the release of intracellular Ca2+ and the influx of external Ca2+, caused by an increase in the rate of removal of cytoplasmic free Ca2+. This increased removal of cytoplasmic Ca2+ from the cell but results from increased Ca2+ uptake into non-mitochondrial stores.

Original languageEnglish (US)
Pages (from-to)10266-10273
Number of pages8
JournalJournal of Biological Chemistry
Volume265
Issue number18
StatePublished - Jul 24 1990

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