Inhibition of Phospholipase A2 Activation in P388D1 Macrophage-Like Cells

  • Keith B. Glaser
  • Mark D. Lister
  • Edward A. Dennis
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

The biosynthesis of eicosanoids is limited by the availability of free arachidonic acid as substrate for the cyclooxygenase and lipoxygenase enzymes. The level of free arachidonic acid in a resting cells is maintained very low (Kunze and Vogt. 1971) and upon stimulation, many cells are capable of releasing arachidonic acid from membrane phospholipids where it is found predominantly esterified in the sn-2 position of the phospholipids. A likely phospholipase candidate for the release of arachidonic acid would be a membrane-associated phospholipase A2 which could directly cleave arachidonic acid from the sn-2 position of membrane phospholipids (Dennis, 1987). However, recently it has become apparent that there are other possible pathways for the release of arachidonic acid in the whole cell. Activation of either phospholipase A1 or phospholipase C coupled with secondary enzymes, lysophospholipase or diacyl glycerol lipase, respectively, would also result in the release of arachidonic acid from membrane phospholipids (Dennis. 1987). Due to the complexity of the possible mechanisms for the release of arachidonic acid, the elucidation of the relevant enzyme(s) involved in the release mechanism depends upon (a) the isolation and characterization of the relevant enzymes. (b) evaluation of specific inhibitors of the relevant enzymes in vitro. (c) correlation of the effects of these inhibitors on the enzymes in vitro with their effects on eicosanoid biosynthesis in the whole cell and (d) demonstration that these inhibitors have little or no effect on the activities of the other enzymes which may be involved in arachidonic acid release (Dennis. 1987).

Keywords

Lipase Prostaglandin Sponge Histidine PGE2 

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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Keith B. Glaser
    • 1
  • Mark D. Lister
    • 1
  • Edward A. Dennis
    • 1
  1. 1.Department of ChemistryUniversity of California at San DiegoLa JollaUSA

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