Plasma membrane hyperpolarization and [Ca2+]i increase induced by fibroblast growth factor in NIH-3T3 fibroblasts: resemblance to early signals generated by platelet-derived growth factor.
The effects of different substances on [Ca2+]i and membrane potential (measured by fura-2 and bis-oxonol fluorescence techniques, respectively) were studied in wild-type and NIH-3T3 fibroblasts transfected with the cDNA encoding the human epidermal growth factor receptor. Application of partially purified PDGF or FGF induced, after a lag (0.5-1 min), a [Ca2+]i increase composed by an initial, slow peak, sustained primarily by intracellular Ca2+ release followed by a plateau, sustained by Ca2+ influx from the medium. The [Ca2+]i changes were paralleled by plasma membrane hyperpolarization mainly due to the activation of a K+ efflux, since raising the extracellular K+ concentration progressively reversed the effect of both growth factors. These responses were much slower than those induced by other agents (bradykinin, extracellular ATP, and EGF). The close resemblance between PDGF- and FGF-induced early signals (time-course and insensitivity to phorbol esters) suggests similar transmembrane signalling mechanisms at the cognate receptor.
Department of Pharmacology, University of Milano, Italy.
A
A
Pandiella
M
M
Magni
J
J
Meldolesi
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D016257:Fura-2; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001572:Benzofurans; D005456:Fluorescent Dyes; D010982:Platelet-Derived Growth Factor; D005346:Fibroblast Growth Factors; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016257:Fura-2