Activation of calcium-insensitive phospholipase A(2) (iPLA(2)) by P2X(7) receptors in murine peritoneal macrophages

Prostaglandins Other Lipid Mediat. 2012 Dec;99(3-4):116-23. doi: 10.1016/j.prostaglandins.2012.09.005. Epub 2012 Oct 2.


Free fatty acid releases are triggered by PLA2 activation and are substrates for many enzymes such as cyclooxygenases. These reactions are responsible for the production of many prostaglandins implicated in the inflammation yet many purinergic receptors have been implicated in diseases characterised by chronic inflammation. The role of P2X receptors was evaluated in LPS-primed murine peritoneal macrophages which were labelled with either [(3)H]-oleic acid or [(3)H]-arachidonic acid. Ten μmolar thapsigargin and 1mM ATP stimulated the release of both unsaturated acids. ATP had no effect at 10 μM and ivermectin had no effect on the response to ATP. The response to ATP was inhibited by magnesium and was not observed with cells from P2X(7)(-/-) mice. The response to ATP was not affected by the removal of extracellular calcium and was inhibited by arachidonyltrifluoromethyl ketone and bromoenol lactone but not by pyrrophenone. The release of the [(3)H]-fatty acids by ATP and thapsigargin was diminished by PD-98058, an inhibitor of MEK-1. It was concluded that in LPS-primed macrophages, P2X(7) receptors, not P2X(4) receptors, activated an iPLA(2) and promoted the release of unsaturated fatty acids secondary to the activation of a kinase. This response might contribute to the inflammation provoked by extracellular ATP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Arachidonic Acid / biosynthesis
  • Arachidonic Acid / metabolism
  • Calcium / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Gene Deletion
  • Ivermectin / pharmacology
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Kinase 1 / antagonists & inhibitors
  • MAP Kinase Kinase 1 / metabolism
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / enzymology
  • Magnesium / metabolism
  • Magnesium / pharmacology
  • Mice
  • Mice, Knockout
  • Oleic Acid / biosynthesis
  • Oleic Acid / metabolism
  • Organic Chemicals / pharmacology
  • Phospholipases A2, Calcium-Independent / metabolism*
  • Purinergic P2 Receptor Agonists / pharmacology*
  • Receptors, Purinergic P2X7 / genetics
  • Receptors, Purinergic P2X7 / metabolism*
  • Thapsigargin / pharmacology
  • Tritium


  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Organic Chemicals
  • PD 98058
  • Purinergic P2 Receptor Agonists
  • Receptors, Purinergic P2X7
  • Tritium
  • Arachidonic Acid
  • Oleic Acid
  • Thapsigargin
  • Ivermectin
  • Adenosine Triphosphate
  • MAP Kinase Kinase 1
  • Map2k1 protein, mouse
  • Phospholipases A2, Calcium-Independent
  • Magnesium
  • Calcium