Inhibition of depolarisation-induced calcium influx into GH3 cells by arachidonic acid: the involvement of protein kinase C.
The influx of 45Ca2+ induced in GH3 cells by exposure to 60 mM K+ medium was inhibited by arachidonic acid (AA) in a concentration-dependent manner. This action of AA was not prevented by inhibitors of its metabolism but was reversed by the inhibitors of protein kinase C (PKC), H7 and staurosporine but not their less active congeners HA 1004 and K252a, respectively. Presumed down-regulation of PKC by pretreatment with phorbol 12,13-dibutyrate (PDBu) also greatly diminished the effect of AA. Experiments to assess effects of AA on 45Ca2+ efflux and on cytosolic Ca2+ concentrations indicated that an additional PKC-independent action of AA involving the release of intracellularly stored calcium was present. Both direct activation of certain PKC isoform(s) by AA and the synergistic influence on PKC activity by its concomitant raising of intracellular Ca2+ concentrations, may be physiologically important in the regulation of depolarisation-induced Ca2+ entry.
MacEwan
D J
DJ
MRC Brain Metabolism Unit, Edinburgh, U.K.
Mitchell
R
R
Thomson
F J
FJ
Johnson
M S
MS
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004563:Electrochemistry; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
D016718:Arachidonic Acid; D011493:Protein Kinase C; D011188:Potassium; D002118:Calcium