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- W1565873079 endingPage "260" @default.
- W1565873079 startingPage "227" @default.
- W1565873079 abstract "PGH synthases catalyze the initial reaction common to the formation of prostanoids and are the target sites for most nonsteroidal anti-inflammatory drugs (NSAIDs). Until the recent discovery of a second PGH synthase isozyme (PGH synthase-2; PGHS-2), it was thought that NSAIDs acted by inhibiting a single enzyme, now referred to as PGH synthase-1 (PGHS-1). It is now believed that PGHS-1 produces prostaglandins that are not directly involved in inflammation, but which regulate “housekeeping” activities; this enzyme is constitutively expressed and, thus, available to respond to rapid transient increases in arachidonate brought about by hormone-induced activation of phospholipases. In contrast, PGHS-2 is the enzyme thought to produce prostaglandins involved in inflammation; this enzyme is not expressed normally, but can be induced in immunoregulatory cells, such as macrophages, and in inflamed tissues, such as fibroblasts and synoviacytes. In addition, anti-inflammatory glucocorticoids and anti-inflammatory cytokines inhibit PGHS-2 induction. It now seems likely that the anti-inflammatory effects of NSAIDs are due primarily to inhibition of PGHS-2. Our current hypothesis is that PGHS-1 and PGHS-2 represent two prostaglandin biosynthetic systems which operate independently; that PGHS-1 and PGHS-2 derive substrate from different arachidonate pools and direct products to different extracellular (PGHS-1) and/or intracellular sites (PGHS-2). These two pathways have evolved to carry out specialized functions; the PGHS-1 pathway to produce prostaglandins that act extracellularly as local hormones to coordinate short-term cellular responses to hormonal stimulation and the PGHS-2 pathway to produce prostaglandins to coordinate prolonged physiological events such as inflammation and mitogenesis." @default.
- W1565873079 created "2016-06-24" @default.
- W1565873079 creator A5025677580 @default.
- W1565873079 creator A5066806044 @default.
- W1565873079 date "1997-01-01" @default.
- W1565873079 modified "2023-10-15" @default.
- W1565873079 title "Prostaglandin endoperoxide synthase isozymes" @default.
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