Linked Life Data

7996454

Source:http://linkedlifedata.com/resource/pubmed/id/7996454

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-1-17
pubmed:abstractText
(S)-N-[2-Cyclohexyl-1-(2-pyridinyl)ethyl]-5-methyl-2-benzoxazolamine+ ++ (BIRM 270) was identified as a potent and enantiomerically selective inhibitor of calcium ionophore A23187-stimulated leukotriene B4 biosynthesis in human neutrophils. The (S)- and (R)-enantiomers exhibited IC50 values of 1 nM and 40 nM, respectively. BIRM 270 did not inhibit 5-lipoxygenase activity in a cell-free assay. In addition, the compound did not interfere with the conversion of exogenous 5-lipoxygenase substrate (15S)-hydroperoxyeicosatetraenoic acid to (5S, 15S)-dihydroxyeicosatetraenoic acid in intact, ionophore-stimulated neutrophils. Under the same experimental conditions, BIRM 270 inhibited the production of 5-lipoxygenase products from endogenous substrate, suggesting that the compound affected arachidonate availability rather than metabolism. Consistent with this concept, the inhibition of leukotriene B4 biosynthesis by BIRM 270 was overcome by the addition of exogenous arachidonic acid to the leukocyte preparation. Direct measurement of free arachidonate by gas chromatography-mass spectrometry confirmed that BIRM 270 inhibited arachidonate release from ionophore-stimulated neutrophils. The compound did not affect arachidonate reacylation. The blockage of arachidonate release coincided with inhibition of leukotriene B4 biosynthesis in these cells. BIRM 270 also inhibited ionophore-stimulated platelet-activating factor biosynthesis by human neutrophils. Although these results suggest that BIRM 270 inhibited phospholipase A2-mediated deacylation of membrane phospholipids, the compound did not directly inhibit the high molecular weight, cytosolic phospholipase A2 derived from human neutrophils or U937 cells. Thus, suppression of arachidonate mobilization by BIRM 270 may be due to indirect inhibition of intracellular phospholipase A2 or to inhibition of another acylhydrolase activity.
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
271
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
1418-26
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
BIRM 270: a novel inhibitor of arachidonate release that blocks leukotriene B4 and platelet-activating factor biosynthesis in human neutrophils.
pubmed:affiliation
Department of Inflammatory Diseases, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
pubmed:publicationType
Journal Article