(±)- Trans -2-(3-methoxy-5-methylsulfonyl-4-propoxyphenyl)-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (L-659,989), a novel, potent PAF receptor antagonist

Ponpipom, Mitree M.; Hwang, San-Bao; Doebber, Thomas W.; Acton, John J.; Alberts, Alfred W.; Biftu, Tesfaye; Brooker, David R.; Bugianesi, Rossana; Chabala, John C.; Gamble, Nancy L.; Graham, Donald W.; Lam, My-Hanh; Wu, Margaret

doi:10.1016/0006-291x(88)90758-9

Cited by 57 publications

(12 citation statements)

References 25 publications

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“…The in vivo potencies of kadsurenone, L-652,731 and L-659,989 compare favourably with potencies in vitro on inhibition of Paf binding to human and rabbit platelet membranes (Ponpipom et al, 1988). We have previously observed that L-652,731 inhibited oedema formation in the Arthus reaction (Hellewell & Williams, 1986;, but not oedema associated with a passive cutaneous anaphylactic reaction .…”

Section: Discussionmentioning

confidence: 67%

“…In these earlier experiments, and those described in the present study, responses to C5a, which has been presumed to be a major mediator in the Arthus reaction, were unaffected by the antagonist. In addition, L-659,989 does not interfere with binding of C5a to its receptor on the neutrophil (Ponpipom et al, 1988).…”

Section: Discussionmentioning

confidence: 92%

“…of Paf. Examples of Pafrelated compounds tested were CV-3988 (Terashita et al, 1983) and SRI 63-675 ; of natural products were BN-52021 (Braquet et al, 1985) and kadsurenone , and synthetic derivatives L-652,731 and L-659,989 (Ponpipom et al, 1988); of synthetic compounds was 48740 RP (Sedivy et al, 1985); and of pharmacological agents was WEB 2086 (CasalsStenzel et al, 1987 Zymosan-activated plasma (ZAP) was used as a source of C5a des Arg. Briefly, rabbit heparinized (10 u ml-1) plasma was incubated with zymosan (5mgml-1) for 30min at 370C followed by centrifugation, twice for 10min at 3000g, to remove the zymosan.…”

Section: Introductionmentioning

confidence: 99%

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Antagonism of Paf‐induced oedema formation in rabbit skin: a comparison of different antagonists

Hellewell

Williams

1989

British J Pharmacology

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Antagonism of Paf‐induced oedema formation in rabbit skin: a comparison of different antagonists

Hellewell

Williams

1989

British J Pharmacology

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“…Kadsurenone, L652,731, and L659,989 specifically compete with PAF for binding to cellular receptors and block PAF-induced activation of platelets and leukocytes Hwang et al, 1985;Hwang et al, 1986;Ponpipom et al, 1988). We rigorously characterized the effects of these antagonists on PAF-induced adhesive responses of neutrophils.…”

Section: Competitive Antagonists Of the Paf Receptor Inhibit Ec-depenmentioning

confidence: 99%

Endothelial cell-associated platelet-activating factor: a novel mechanism for signaling intercellular adhesion.

Zimmerman

McIntyre

Mehra

et al. 1990

The Journal of Cell Biology

357

153

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Abstract. The binding of neutrophils (polymorphonuclear leukocytes [PMNs]) to endothelial cells (ECs) presents special requirements in the regulation of intercellular adhesion. ECs that are stimulated by certain agonists, including thrombin and cytokines (tumor necrosis factor or, interleukin-1), generate molecular signals that induce the adhesion of PMNs (endothelial cell-dependent neutrophil adhesion). Our experiments demonstrate that the mechanism of binding induced by thrombin is distinct from that induced by the cytokines based on the time courses, the requirement for protein synthesis, and differential binding of HL60 promyelocytic leukemia cells to ECs activated by the two classes of agonists. The rapid EC-dependent PMN adhesion (initiated in minutes) that occurs when the ECs are stimulated by thrombin is temporally coupled with the accumulation of platelet-activating factor, a biologically active phosphoglyceride that remains associated with ECs and that activates PMNs by binding to a cell surface receptor. A portion of the newly synthesized plateletactivating factor (PAF) is on the EC surface, as demonstrated by experiments in which the rate of hydrolysis of PAF synthesized by activated ECs was accelerated by extracellular PAF acetylhydrolase. When ECs were treated with exogenous PAF they became adhesive for PMNs; the PMN binding was prevented by incubating the ECs with PAF acetylhydrolase or by treating the PMNs with competitive PAF receptor antagonists. Thus PAF associated with the EC plasma membrane induces PMN binding, an observation supported by experiments in which PAF in model membranes (liposomes) stimulated rapid PMN adhesion to ECs and to cell-free surfaces. In addition, competitive antagonists of the PAF receptor inhibited the binding of PMNs to ECs activated by thrombin and other rapidly acting agonists, but not to ECs activated by tumor necrosis factor c~, indicating that PAF that is endogenously synthesized by ECs can mediate neutrophil adhesion. These experiments demonstrate a novel mechanism by which a cell-associated phospholipid, PAF, can serve as a signal for an intercellular adhesive event.

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“…Based on this model, a large number of PAF antagonists has been identified in the past few years. These substances include structural analogues of PAF and compounds chemically unrelated to PAF [2,10,12,21,31,35,37]. The structure of SR 27417 (fumarate salt) N-(2-dimethy- [6,18,[22][23][24], belonging to a newly developed series of PAF antagonists, has been described as being one of the most potent PAF receptor antagonist known to date when compared with other PAF antagonists [22].…”

Section: Introductionmentioning

confidence: 99%

In vitro inhibitory effect of SR 27417, a potent platelet-activating factor (PAF) receptor antagonist, on the PAF-induced bovine platelet aggregation

et al. 2000

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-The in vitro inhibitory effect of SR 27417, an antagonist of the platelet-activating factor (PAF) receptor, on PAF-induced platelet aggregation was studied in blood collected from seven healthy Friesien calves. Inhibitory effects of SR 27417 were determined at thirteen different concentrations (0.1 -400 nM) by using the dose-response curves of PAF on calf platelet aggregation. In the presence of SR 27417, the maximal slopes of aggregation (%/min) induced by low and high concentrations of PAF were significantly different from the control values obtained without an antagonist at p ≤ 0.05 and p ≤ 0.01 respectively. In vitro PAF-induced calf platelet aggregation was dosedependently inhibited by SR 27417. The drug inhibited PAF-induced platelet aggregation in a competitive reversible manner (pA 2 = 10.46 ± 2.36 mol . L -1 ). In conclusion, the results of our study showed that addition of SR 27417 to bovine platelet in vitro inhibits PAF-induced platelet aggregation. bovine / platelet / platelet aggregation / platelet-activating factor (PAF) / SR 27417Résumé -Effet inhibiteur in vitro du SR 27417, un puissant antagoniste du récepteur du facteur d'activation plaquettaire sur l'agrégation des plaquettes induite par le PAF chez le bovin. L'effet inhibiteur in vitro du SR 27417, un antagoniste du récepteur du facteur d'activation plaquettaire (PAF) induite par le PAF sur l'agrégation plaquettaire a été étudiée dans le sang prélevé des sept veaux sains de race Frisonne. L'effet inhibiteur du SR 27417 a été déterminé avec treize concentrations différentes (0,1 -400 nM) en utilisant les courbes dose-effet du PAF sur l'agrégation Vet. Res. 31 (2000) 267-272 267

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(±)- Trans -2-(3-methoxy-5-methylsulfonyl-4-propoxyphenyl)-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (L-659,989), a novel, potent PAF receptor antagonist

Cited by 57 publications

References 25 publications

Antagonism of Paf‐induced oedema formation in rabbit skin: a comparison of different antagonists

Antagonism of Paf‐induced oedema formation in rabbit skin: a comparison of different antagonists

Endothelial cell-associated platelet-activating factor: a novel mechanism for signaling intercellular adhesion.

In vitro inhibitory effect of SR 27417, a potent platelet-activating factor (PAF) receptor antagonist, on the PAF-induced bovine platelet aggregation

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