RGD Reference Report - Platelet activating factor (PAF) and tumor necrosis factor-alpha (TNF alpha) interactions in endotoxemic shock: studies with BN 50739, a novel PAF antagonist. - Rat Genome Database

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Platelet activating factor (PAF) and tumor necrosis factor-alpha (TNF alpha) interactions in endotoxemic shock: studies with BN 50739, a novel PAF antagonist.

Authors: Rabinovici, R  Yue, TL  Farhat, M  Smith EF, 3RD  Esser, KM  Slivjak, M  Feuerstein, G 
Citation: Rabinovici R, etal., J Pharmacol Exp Ther. 1990 Oct;255(1):256-63.
RGD ID: 10449465
Pubmed: PMID:2213560   (View Abstract at PubMed)

BN 50739, a new PAF receptor antagonist, was tested in vitro and in vivo for its capacity to block PAF, endotoxin and recombinant human tumor necrosis factor-alpha (rTNF)-mediated effects. In vitro, BN 50739 blocked PAF-induced platelet aggregation by 60 to 100% at 0.2-1 x 10(-7) M (P less than .002), respectively. In the conscious rat, pretreatment (30 min) with BN 50739 (n = 5-13) dose-dependently attenuated PAF-induced hypotension (-5 +/- 5 vs. - 43 +/- 2 mm Hg, P less than .01) and shortened the recovery time of mean arterial pressure (22 +/- 13 vs. 325 +/- 46 sec, P less than .01). BN 50739 (10 mg/kg i.p., n = 5-11) prevented endotoxin (14.4 mg/kg) induced-hemoconcentration (54 +/- 1 vs. 46 +/- 1%, P less than .01) and reduced 24-hr mortality (100 vs. 60%, P less than .05). Only partial protection was conveyed by BN 50739 against the hypotensive response to endotoxin (115 +/- 3 vs. 91 +/- 4 mm Hg, P less than .03). Also, BN 50739 attenuated the lipopolysaccharide-induced elevation of plasma thromboxane B2 (21.2 +/- 0.8 vs. 46.7 +/- 11.8 pg/100 microliters, P less than .01) and tumor necrosis factor-alpha (7523 +/- 3983 vs. 26,430 +/- 3541 U/ml, P less than .05), whereas leukopenia and thrombocytopenia remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
toxic shock syndrome treatmentISOTnf (Rattus norvegicus)10449465; 10449465 RGD 
toxic shock syndrome treatmentIEP 10449465 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)


Additional Information