Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0003695,
umls-concept:C0014264,
umls-concept:C0025519,
umls-concept:C0027950,
umls-concept:C0030685,
umls-concept:C0031667,
umls-concept:C0036974,
umls-concept:C0038952,
umls-concept:C0086418,
umls-concept:C0381876,
umls-concept:C0391871,
umls-concept:C0591833,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1963578,
umls-concept:C1999216
|
| pubmed:issue |
3
|
| pubmed:dateCreated |
1995-10-25
|
| pubmed:abstractText |
Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 fatty acyl group [predominantly arachidonic acid (AA)] of membrane phospholipids, the products of which are further metabolized, forming a variety of eicosanoids and/or platelet-activating factor. PLA2 activity is significantly enhanced during inflammation and therefore offers an intriguing target in designing anti-inflammatory drugs. SB 203347 (2-[2-[3,5-bis (trifluoromethyl) sulfonamido]-4- trifluoromethylphenoxy] benzoic acid) potently inhibits rh type II 14 kDa PLA2 (IC50 = 0.5 microM) but exhibits a 40-fold weaker inhibition of 85 kDa PLA2 (IC50 = 20 microM) using [3H]-AA E. coli as substrate. A specific interaction with rh type II 14 kDa PLA2 was confirmed both by observing the pH dependence of its IC50 and by demonstrating linear inhibition in a "scooting" kinetic model using radiolabeled phospholipid reporter substrate in a 1,2-dimyristoyl phosphatidylmethanol vesicle. Before evaluating the effect of SB 203347 on AA metabolism in intact human neutrophil, we showed that it fully inhibits PLA2 activity in acid extracted-intact human neutrophil homogenate (IC50 = 4.7 microM). SB 203347 inhibited A23187-induced intact human neutrophil AA mass release in a concentration-dependent manner (IC50 = 1 microM), which coincided with reductions in the biosynthesis of platelet-activating factor (IC50 = 1.5 microM) and leukotriene B4 (IC50 = 2.3 microM). Finally, SB 203347 prolonged survival in a mouse model of endotoxin shock delivered i.p. Taken together, the data support a role of cellular 14 kDa PLA2 in the formation of AA-derived proinflammatory lipid mediator.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Alkyl-2-acetylglycerophosphocholin...,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene B4,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Activating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
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| pubmed:issn |
0022-3565
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
274
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
N
|
| pubmed:pagination |
1254-62
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:7562496-1-Alkyl-2-acetylglycerophosphocholine Esterase,
pubmed-meshheading:7562496-Animals,
pubmed-meshheading:7562496-Arachidonic Acid,
pubmed-meshheading:7562496-Cell-Free System,
pubmed-meshheading:7562496-Disease Models, Animal,
pubmed-meshheading:7562496-Enzyme Inhibitors,
pubmed-meshheading:7562496-Humans,
pubmed-meshheading:7562496-Leukotriene B4,
pubmed-meshheading:7562496-Lipopolysaccharides,
pubmed-meshheading:7562496-Male,
pubmed-meshheading:7562496-Mice,
pubmed-meshheading:7562496-Mice, Inbred C57BL,
pubmed-meshheading:7562496-Neutrophils,
pubmed-meshheading:7562496-Phospholipases A,
pubmed-meshheading:7562496-Phospholipases A2,
pubmed-meshheading:7562496-Platelet Activating Factor,
pubmed-meshheading:7562496-Shock, Septic,
pubmed-meshheading:7562496-Sulfonamides,
pubmed-meshheading:7562496-Survivors
|
| pubmed:year |
1995
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| pubmed:articleTitle |
SB 203347, an inhibitor of 14 kDa phospholipase A2, alters human neutrophil arachidonic acid release and metabolism and prolongs survival in murine endotoxin shock.
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| pubmed:affiliation |
Department of Inflammation & Respiratory Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA.
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| pubmed:publicationType |
Journal Article
|