Arachidonic acid activates Ca2+ extrusion in macrophages.
Stimulation of macrophages with platelet-activating factor (PAF) elicits an increase of intracellular calcium concentration, Ca2+i, which was monitored here at the single cell level with the calcium-sensitive dye Fura-2. The sustained component of this Ca2+i increase reflects the dynamic balance achieved between enhanced Ca2+ influx and efflux. In macrophages where a steady increase of Ca2+i has been evoked by 50 nM thapsigargin (a molecule known to empty Ca2+ stores and elevate Ca2+i in various cell types), PAF activates Ca2+ efflux, without causing a preceding increase in Ca2+i. This result shows that in this case, Ca2+ extrusion is not merely a consequence of a Ca2+i increase. PAF-evoked Ca2+ extrusion does not result from the activation of the Na+/Ca2+ exchanger. Exogenous arachidonic acid (10-100 microM) elicits Ca2+ efflux in macrophages where Ca2+i has been previously elevated by either PAF or thapsigargin. PAF-induced Ca2+ extrusion is blocked by 4-bromophenacylbromide, an inhibitor of arachidonic acid production by phospholipase A2. Together, these results suggest that arachidonic acid, which is produced in PAF-stimulated macrophages, contributes to the regulation of a Ca2+ extrusion system, which is presumably a Ca2(+)-ATPase.
Randriamampita
C
C
Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris, France.
Trautmann
A
A
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009712:Nucleotides, Cyclic / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D001095:Arachidonic Acids; D002352:Carrier Proteins; D009712:Nucleotides, Cyclic; D010972:Platelet Activating Factor; D019831:Sodium-Calcium Exchanger; D013729:Terpenes; D016718:Arachidonic Acid; D019284:Thapsigargin; D012964:Sodium; D011493:Protein Kinase C; D000252:Calcium-Transporting ATPases; D002118:Calcium