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, Volume 41, Issue 1–2, pp 111–113 | Cite as

Groups I, II and III extracellular phospholipases A2: Selective inhibition of group II enzymes by indomethacin but not other NSAIDs

  • Isabel Benito Lobo
  • J. R. S. Hoult
Papers Presented at the Joint Meeting of the European Inflammation Society and Hungarian Biochemical Society Balatonaliga, Hungary, 19–21 May, 1993

Abstract

The three types (groups I, II and III) of stable extracellular 14 kDa phospholipase A2 enzymes differ in their primary amino acid sequences and their properties. It may thus be possible to design low-molecular weight inhibitors targeted to the secretory form of mammalian PLA2. this enzyme has been implicated in inflammatory disorders. We have studied the inhibition of four distinct PLA2 enzymes by a range of NSAIDs, using3H-oleate release from prelabelled membranes ofE. coli for assay. The enzymes used were cobra venom PLA2 (Naja naja, a group I enzyme), bee venom PLA2 (Apis mellifera, group III), recombinant human synovial PLA2 (group II) and rat peritoneal PLA2 (group II). Under the conditions of the3H-oleateE. coli assay, 1 mM concentrations of aspirin, sodium salicylate, paracetamol (acetaminophen), oxphenbutazone, ibuprofen, flurbiprofen and nabumetone failed to inhibit significantly any of the four enzymes. However, indomethacin inhibited all four enzymes, although effects were greatest on the two group II enzymes (rat peritoneal and human synovial PLA2). Approximate IC50 values were 28 and 35 μM, respectively. Inhibition by indomethacin was not time dependent and was greater at micromolar rather than millimolar levels of calcium. We conclude that indomethacin but not the other tested classes of NSAID inhibits the group II PLA2 enzyme in a selective manner and suggest that this may be relevant both to its clinical spectrum and to the design of novel pharmaceutical leads.

Key words

Phospholipase A2 Aspirin Indomethacin NSAIDs Bee venom 

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Copyright information

© Birkhäuser Verlag 1994

Authors and Affiliations

  • Isabel Benito Lobo
    • 1
  • J. R. S. Hoult
    • 1
  1. 1.Pharmacology GroupKing's CollegeLondonUK

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