INHIBITION OF CONSTITUTIVE AND INDUCIBLE CYCLOOXYGENASE ACTIVITY IN HUMAN PLATELETS AND MONONUCLEAR-CELLS BY NSAIDS AND COX-2 INHIBITORS

A range of NSAIDs and reported Cox 2 selective compounds were tested i n human freshly isolated platelets and LPS-stimulated mononuclear cell s to determine their potency and selectivity as inhibitors of constitu tive (presumably Cox 1) and inducible (presumably Cox 2) cyclooxygenas e respectively. All compounds tested were either equipotent at inhibit ing constitutive and inducible cyclooxygenase or were selective for th e inducible form. The most selective compound was Dup697 and the least selective, ketoprofen. Several compounds only produced a partial inhi bition of constitutive cyclooxygenase as the maximum inhibitor concent ration achievable in the assay was limited to 1 mM. With the exception of paracetamol, all compounds were able to produce full inhibition cu rves against the inducible form. Potency estimates against constitutiv e Cox compare closely with published data but most compounds were cons istently more potent against the inducible isoform than in published d ata for human cloned, microsomal Cox 2. These data suggest that human mononuclear cells are either exquisitely sensitive to some NSAIDs or t hey may contain another Cox isoform as yet indistinguishable from Cox 2.