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Effect on Non‐steroidal Anti‐inflammatory Drugs on Arachidonic Acid Metabolism
Author(s) -
Siegel Marvin I.
Publication year - 1981
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/j.1526-4610.1981.hed2106264.x
Subject(s) - chemistry , lipoxygenase , arachidonic acid , cyclooxygenase , sephadex , biochemistry , enzyme , prostaglandin , sodium salicylate , metabolism , pharmacology , biology , organic chemistry
SYNOPSIS The enzymes of arachidonic acid metabolism via the lipoxygenase pathway in human platelets have been characterized and partially purified. Two separable lipoxygenase activities can be detected by chromatography on Sephadex G‐150 and DEAE‐Sephadex. One of these has an apparent molecular weight (M r ) of 100,000. A second enzyme species behaves as an M r 160,000 entity containing, in addition to lipoxygenase, a peroxidase activity that catalyzes the conversion of 12L‐hydro‐peroxy‐5,8,10,14‐icosatetraenoic acid (HPETE) to 12L‐hydroxy‐5,8,10,14‐icosatetraenoic acid (HETE). Aspirin, indomethacin, sodium salicylate, phenylbutazone, ibuprofen, naproxen, and sulindac, but not acetaminophen or phenacetin, give rise to increased levels of HPETE in the lipoxygenase pathway. This increase in HPETE levels is the result of the ability of these drugs to directly inhibit the enzymatic conversion of HPETE to HETE. The labile lipoxygenase produced HPETE stimulates its own production by increasing lipoxygenase activity; HETE does not share this activity. In addition, HPETE strongly suppresses prostaglandin and thromboxane production by inhibiting cyclo‐oxygenase (prostaglandin synthetase). The ability of sodium salicylate, which does not inhibit cyclo‐oxygenase in vitro, to elevate levels of HPETE may account for its ability to inhibit prostaglandin production in vivo . Moreover, since HPETE's are precursors of slow reacting substance of anaphylaxis, the acute responses to aspirin and other anti‐inflammatory drugs observed in certain sensitive individuals may be the result of these patients' extreme sensitivity to HPETE peroxidase inhibition or the resultant rise in HPETE concentration.