Linked Life Data

2439626

Source:http://linkedlifedata.com/resource/pubmed/id/2439626

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1987-8-21
pubmed:abstractText
The allergic mediator release inhibitor 3,7-dimethoxy-4-phenyl-N-1H-tetrazol-5-yl-4H-furo[3,2-b]indole-2- carboxamide, L-arginate (CI-922) is a potent inhibitor of human neutrophil functions in vitro. Over a concentration range from 1 to 100 mumol CI-922 inhibits the chemotactic response of neutrophils to the synthetic chemotaxin N-formyl-methionyl-leucyl-phenylalanine (FMLP). CI-922 also inhibits respiratory and secretory responses of neutrophils in response to agents that stimulate phospholipase C-dependent phosphoinositide hydrolysis to generate the second messengers inositol 1,4,5, trisphosphate and 1,2 diacylglycerol, including: the plasma membrane receptor-specific ligands FMLP and C5a; serum-opsonized zymosan; concanavalin A; and the guanine nucleotide regulatory protein-specific stimulus guanosine-5'-0-(3-thiotriphosphate) (GTP gamma S). CI-922 also inhibits neutrophil functions stimulated by the calcium ionophore A23187. In contrast, CI-922 does not inhibit neutrophil responses to protein kinase C-specific stimuli such as phorbol 12-myristate 13-acetate (PMA) or L-alpha-1,2 dioctanoylglycerol (DiC8). CI-922 also fails to inhibit the synergistic activation of the respiratory burst by suboptimal concentrations of PMA and calcium ionophore A23187. The observation that CI-922 inhibits neutrophil responses to a variety of soluble and particulate stimuli, excluding protein kinase C-specific stimuli, allows us to postulate the site of action of the compound. We propose that CI-922 inhibits neutrophil activation at a site distal to signal transduction through the guanine nucleotide regulatory protein required for second messenger generation but proximal to phosphorylation reactions mediated by protein kinase C and calmodulin-dependent protein kinases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0741-5400
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Inhibition of human neutrophil activation by the allergic mediator release inhibitor, CI-922: differential inhibition of responses to a variety of stimuli.
pubmed:publicationType
Journal Article, Comparative Study