| | |  | | | | Record from Web of Science® | | | | | | |
| DIFFERENTIAL INHIBITION OF PROSTAGLANDIN ENDOPEROXIDE SYNTHASE (CYCLOOXYGENASE) ISOZYMES BY ASPIRIN AND OTHER NONSTEROIDAL ANTIINFLAMMATORY DRUGS |
|
|
| Author(s): MEADE EA, SMITH WL, DEWITT DL |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 268 Issue: 9 Pages: 6610-6614 Published: MAR 25 1993 |
| Times Cited: 973 References: 36 |
| 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. MICHIGAN STATE UNIV, DEPT BIOCHEM, 510 BIOCHEM BLDG, E LANSING, MI 48824 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: KT368 |
| ISSN: 0021-9258 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |