Arachidonic acid mediates calcium influx induced by basic fibroblast growth factor in Balb-c 3T3 fibroblasts.
Basic fibroblast growth factor (bFGF), a peptide acting as a mitogen in different cell types, is able to induce a long lasting non capacitative calcium influx from the extracellular medium in Balb-c 3T3 mouse fibroblasts. This effect is mediated by the tyrosine kinase activity of bFGF receptors and the opening of voltage independent, agonist activated calcium channels. In this paper we investigate the signal transduction steps involved in this process using single cell calcium fluorimetry and electrophysiological techniques. One of the pathways initiated by the binding of growth factors to their tyrosine kinase receptors is the activation of cytosolic phospholipase A2 (cPLA2) and the release of arachidonic acid (AA) from the plasma membrane with the subsequent production of eicosanoids. We show here that, in our preparation, this pathway is involved in the opening of the bFGF-activated calcium permeable channels, through the activation of mitogen activated protein kinase (MAPK) and cPLA2. Evidence for direct involvement of AA is given by the finding that: (i) bFGF induces AA release from Balb-c 3T3 cells; (ii) blockers of AA metabolism are not effective; and (iii) the application of either arachidonic acid or its non metabolizable analogue 5,8,11,14-eicosatetraynoic acid (ETYA) reproduces the responses described for bFGF. Finally, single channel analysis indicates that bFGF, AA and ETYA can activate the same calcium permeable channel.
Munaron
L
L
Department of Animal Biology, University of Torino, Italy. munaron@dm.unito.it
Antoniotti
S
S
Distasi
C
C
Lovisolo
D
D
D016475:3T3 Cells; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005470:Fluorometry; D051379:Mice; D018408:Patch-Clamp Techniques; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D001095:Arachidonic Acids; D015220:Calcium Channels; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D015117:5,8,11,14-Eicosatetraynoic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium