Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells

Eur J Pharmacol. 1998 Apr 17;347(1):87-94. doi: 10.1016/s0014-2999(98)00078-8.

Abstract

Recent studies have shown that cyclooxygenase exists in two isozyme forms. Since differences in the pharmacological profiles of nonsteroidal anti-inflammatory drugs (NSAIDs) might be accounted for by varying degrees of selectivity for these isozymes, cyclooxygenase-1 and -2, the relative potency of various NSAIDs in inhibiting their activities was examined in intact human cells. We used human platelets cyclooxygenase-1 and interleukin-1beta-stimulated human synovial cell cyclooxygenase-2 for measuring cyclooxygenase selectivity. The presence of the enzymes was confirmed by immunoblotting and immunoprecipitation analysis, and by the reverse transcriptase-polymerase chain reaction. Mean IC50 values (microM) for human platelet cyclooxygenase-1 and interleukin-1beta-stimulated human synovial cell cyclooxygenase-2 and cyclooxygenase-1/-2 IC50 ratio of various NSAIDs were as follows: aspirin, 3.2, 26, 0.12; diclofenac, 0.037, 0.00097, 38; etodolac, 122, 0.68, 179; ibuprofen, 3.0, 3.5, 0.86; indomethacin, 0.013, 0.044, 0.30; loxoprofen (active metabolite), 0.38, 0.12, 3.2; NS-398, 12, 0.0095, 1263; oxaprozin, 2.2, 36, 0.061; zaltoprofen, 1.3, 0.34, 3.8; respectively. Our bioassay system employing intact human cells to assess the cyclooxygenase selectivity of NSAIDs may provide clinically useful information.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blood Platelets / drug effects*
  • Blood Platelets / enzymology*
  • Blood Platelets / metabolism
  • Blotting, Western
  • Cells, Cultured
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Cytokines / pharmacology
  • Dinoprostone / biosynthesis
  • Humans
  • Isoenzymes / blood
  • Isoenzymes / drug effects
  • Isoenzymes / metabolism*
  • Membrane Proteins
  • Polymerase Chain Reaction
  • Precipitin Tests
  • Prostaglandin-Endoperoxide Synthases / blood
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Synovial Membrane / drug effects*
  • Synovial Membrane / enzymology*
  • Synovial Membrane / metabolism
  • Transcription, Genetic

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Cytokines
  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone