Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs.

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Meade EA, Smith WL, DeWitt DL

Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs.

J Biol Chem. 1993 Mar 25;268(9):6610-4.

PubMed ID

8454631 [ View in PubMed

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Abstract

Murine prostaglandin endoperoxide (PGH) synthase-1 and PGH synthase-2 expressed in cos-1 cells were found to be differentially sensitive to inhibition by common nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin completely inhibited bis-oxygenation of arachidonate by PGH synthase-1; in contrast, aspirin-treated PGH synthase-2 metabolized arachidonate primarily to 15-hydroxyeicosatetraenoic acid (15-HETE) instead of PGH2. ID50 values were determined for a panel of common NSAIDs by measuring instantaneous inhibition of cyclooxygenase activity using an oxygen electrode. Among common NSAIDs tested, indomethacin, sulindac sulfide, and piroxicam preferentially inhibited PGH synthase-1; ibuprofen, flurbiprofen, and meclofenamate inhibited both enzymes with comparable potencies; and 6-methoxy-2-naphthylacetic acid preferentially inhibited PGH synthase-2. These results demonstrate that the two PGH synthases are pharmacologically distinct and indicate that it may be possible to develop isozyme-specific cyclooxygenase inhibitors useful both for anti-inflammatory therapy and for delineating between the biological roles of the PGH synthase isozymes.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Meclofenamic acid	Prostaglandin G/H synthase 1	Protein	Humans	Yes	Inhibitor	Details