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, Volume 39, Supplement 1, pp C39–C42 | Cite as

Secretory phospholipase A2 inhibitors and calmodulin antagonists as inhibitors of cytosolic phospholipase A2

  • William C. Hope
  • Ting Chen
  • Douglas W. Morgan
Drugs and Lipid Mediators


Human cytosolic phospholipase A2 (cPLA2, 85 kDa) appears to be pharmacologically distinct from human secretory phospholipase A2 (sPLA2, 14 kDa). Marine natural products and PLA2 substrate and product analogs were potent inhibitors of human recombinant sPLA2 (r-sPLA2), whereas these compounds stimulated, weakly inhibited, or had no effect on cPLA2 activity from the human monocytic cell line U937. In contrast, within a series of seven reported calmodulin (CaM) antagonists tested, significant correlations among the rank order of potencies of these compounds as inhibitors of cPLA2, r-sPLA2, and a CaM-dependent phosphodiesterase were observed. The correlated inhibitory effects of the hydrophobic CaM antagonists on cPLA2 and sPLA2 may reflect a common feature (possibly a hydrophobic domain) shared by these two types of enzymes.


Potent Inhibitor Rank Order Phosphodiesterase Monocytic Cell Hydrophobic Domain 
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  1. [1]
    J. D. Clark, N. Milona and J. L. Knopf,Purification of a 110-kilodalton cytosolic phospholipase A 2 from the human monocytic cell line U937. Proc. Natl. Acad. Sci.87, 7708–7712 (1990).PubMedGoogle Scholar
  2. [2]
    R. M. Kramer, E. F. Roberts, J. Manetta and J. E. Putnam,The Ca 2+-sensitive cytosolic phospholipase A 2 is a 100-kDa protein in human monoblast U937 cells. J. Biol. Chem.266, 5268–5272 (1991).PubMedGoogle Scholar
  3. [3]
    M. T. Withnall, T. J. Brown and B. K. Diocee,Calcium regulation of phospholipase A 2 is independent of calmodulin. Biochem. Biophys. Res. Commun.121, 507–513 (1984).CrossRefPubMedGoogle Scholar
  4. [4]
    H. Krause, P. Dieter, A. Schulze-Specking, A. Ballhorn, E. Ferber and K. Decker,Synergistic effect of magnesium and calcium ions in the activation of phospholipase A 2 of liver macrophages. Biochem. Biophys. Res. Commun.175, 532–536 (1991).CrossRefPubMedGoogle Scholar
  5. [5]
    K. I. Hulkower, W. C. Hope, T. Chen, C. M. Anderson, J. W. Coffey and D. M. Morgan,Interleukin-1β stimulates cytosolic phospholipase A 2 in rheumatoid synovial fibroblasts. Biochem. Biophys. Res. Commun.184, 712–718 (1992).CrossRefPubMedGoogle Scholar
  6. [6]
    W. C. Hope, B. J. Patel, C. Fiedler-Nagy and B. H. Wittreich,Retinoids inhibit phospholipase A 2 in human synovial fluid and arachidonic acid release from rat peritoneal macrophages. Inflammation14, 543–559 (1990).CrossRefPubMedGoogle Scholar
  7. [7]
    W. Levin, R. F. Daniel, C. R. Stoner, T. J. Stoller, J. A. W. Swanson, Y. M. Angelillo, P. C. Familletti and R. M. Crowl,Purification of recombinant human secretory phospholipase A 2 (group II) produced in long-term immobilized cell culture. Protein Expression and Purification3, 27–35 (1992).PubMedGoogle Scholar
  8. [8]
    A. F. Welton, W. C. Hope and G. Wiggan,Studies on the ability of calmodulin antagonists to inhibit, a soluble phospholipase A 2 from snake venom InAdv. Cyclic Nucleotide Protein Phosphorylation Res., vol. 17A (Ed. P. Greengard), p. 76, Raven Press, New York 1983.Google Scholar

Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • William C. Hope
    • 1
  • Ting Chen
    • 1
  • Douglas W. Morgan
    • 1
  1. 1.Department of Bronchopulmonary ResearchHoffmann-La Roche Inc.NutleyUSA

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