| pubmed-article:7872783 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:7872783 | lifeskim:mentions | umls-concept:C0389003 | lld:lifeskim |
| pubmed-article:7872783 | lifeskim:mentions | umls-concept:C0033541 | lld:lifeskim |
| pubmed-article:7872783 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:7872783 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:7872783 | lifeskim:mentions | umls-concept:C0763297 | lld:lifeskim |
| pubmed-article:7872783 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:7872783 | pubmed:dateCreated | 1995-3-29 | lld:pubmed |
| pubmed-article:7872783 | pubmed:abstractText | Aspirin causes a time-dependent inhibition of prostaglandin endoperoxide H synthases (PGHS)-1 and -2 by acetylating active site serines present in both isozymes. In the case of PGHS-1, aspirin acetylation blocks cyclooxygenase activity, apparently by preventing arachidonate binding to the cyclooxygenase active site. With PGHS-2, acetylation does not block substrate binding but rather alters the enzyme in such a way that the acetylated form of PGHS-2 produces 15R-hydroxyeicosatetraenoic acid (15R-HETE) instead of the usual prostaglandin endoperoxide product. Based on these differences between PGHS-1 and PGHS-2, we reasoned that a salicylate ester containing an acyl group somewhat larger than the acetyl group of aspirin might be a selective inhibitor of PGHS-2. Accordingly, we prepared and tested eight different acyl salicylates as inhibitors of human (h) PGHS-1 and -2 expressed transiently in cos-1 cells. Valeryl(pentanoyl)salicylate (VSA) was the only compound in this series which showed isozyme selectivity, and, surprisingly, VSA inhibited hPGHS-1 much more effectively than hPGHS-2. Inhibition of hPGHS-1 by VSA was time-dependent. VSA also inhibited ovine PGHS-1 but did not inhibit the S530A mutant of ovine PGHS-1. This latter mutant, which lacks the active site serine hydroxyl group, is also refractory to inhibition by acetylsalicylate. Thus, we conclude that VSA acylates the active site serine of PGHS-1. VSA inhibited prostanoid synthesis by serum-starved murine NIH 3T3 cells which express only PGHS-1; in contrast, VSA caused only partial inhibition of prostanoid synthesis by serum-stimulated 3T3 cells which express both PGHS isozymes. Our results establish that VSA can be used as a reasonably selective inhibitor of PGHS-1. | lld:pubmed |
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| pubmed-article:7872783 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:7872783 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:7872783 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:7872783 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:7872783 | pubmed:issn | 0003-9861 | lld:pubmed |
| pubmed-article:7872783 | pubmed:author | pubmed-author:DunnJJ | lld:pubmed |
| pubmed-article:7872783 | pubmed:author | pubmed-author:SmithW LWL | lld:pubmed |
| pubmed-article:7872783 | pubmed:author | pubmed-author:Bhattacharyya... | lld:pubmed |
| pubmed-article:7872783 | pubmed:author | pubmed-author:LecomteMM | lld:pubmed |
| pubmed-article:7872783 | pubmed:author | pubmed-author:MorgansD JDJ | lld:pubmed |
| pubmed-article:7872783 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:7872783 | pubmed:day | 20 | lld:pubmed |
| pubmed-article:7872783 | pubmed:volume | 317 | lld:pubmed |
| pubmed-article:7872783 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:7872783 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:7872783 | pubmed:pagination | 19-24 | lld:pubmed |
| pubmed-article:7872783 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:7872783 | pubmed:meshHeading | pubmed-meshheading:7872783-... | lld:pubmed |
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| pubmed-article:7872783 | pubmed:meshHeading | pubmed-meshheading:7872783-... | lld:pubmed |
| pubmed-article:7872783 | pubmed:year | 1995 | lld:pubmed |
| pubmed-article:7872783 | pubmed:articleTitle | Selective inhibition of prostaglandin endoperoxide synthase-1 (cyclooxygenase-1) by valerylsalicylic acid. | lld:pubmed |
| pubmed-article:7872783 | pubmed:affiliation | Department of Biochemistry, Michigan State University, East Lansing 48824. | lld:pubmed |
| pubmed-article:7872783 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:7872783 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
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