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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1993-1-22
|
| pubmed:abstractText |
LY223982, (E)-5-(3-carboxybenzoyl)-2-((6-(4-methoxyphenyl)-5- hexenyl)oxy)benzenepropanoic acid, is a newly discovered potent inhibitor of specific binding of leukotriene B4 (LTB4) to its receptor on human neutrophils. This study demonstrated that the compound is also a specific antagonist of LTB4-induced neutrophil activation under both in vitro and in vivo conditions. LY223982 was found to be 189-fold more effective in displacing [3H]LTB4 than 35S-N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) from their corresponding receptors on human neutrophils. The concentration inhibiting 50% of response (IC50) for displacement of [3H]LTB4 (13.2 nM) was only 6.8-fold higher than the value for nonradioactive LTB4. The compound inhibited the aggregation of guinea pig neutrophils caused by LTB4 more strongly than FMLP or platelet-activating factor. The IC50 for inhibition of LTB4-induced responses (74 nM) was 93- and > 135-fold lower than the IC50 for inhibition of the corresponding FMLP and platelet-activating factor-induced effects. LY223982 was also a potent antagonist of the aggregation of human neutrophils by LTB4 (IC50, 100 nM). Chemotaxis of human neutrophils induced by LTB4 was only modestly inhibited by the compound (IC50 = 6 microM) but it had even less effect on cell movement caused by FMLP. LY223982 inhibited transient leukopenia induced in rabbits with LTB4 (ED50, 3 mg/kg) but not with FMLP. It had no agonist activity in any of the test systems. In summary, the results indicate that LY223982 is a potent specific antagonist of LTB4-induced neutrophil activation.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0022-3565
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
263
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1009-14
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:1335049-Animals,
pubmed-meshheading:1335049-Benzophenones,
pubmed-meshheading:1335049-Cell Aggregation,
pubmed-meshheading:1335049-Chemotaxis, Leukocyte,
pubmed-meshheading:1335049-Female,
pubmed-meshheading:1335049-Guinea Pigs,
pubmed-meshheading:1335049-Humans,
pubmed-meshheading:1335049-Leukopenia,
pubmed-meshheading:1335049-Leukotriene B4,
pubmed-meshheading:1335049-Male,
pubmed-meshheading:1335049-N-Formylmethionine Leucyl-Phenylalanine,
pubmed-meshheading:1335049-Neutrophils,
pubmed-meshheading:1335049-Rabbits
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
Specific inhibition of leukotriene B4-induced neutrophil activation by LY223982.
|
| pubmed:affiliation |
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana.
|
| pubmed:publicationType |
Journal Article
|