Platelet Activating Factor Antagonists

Summers, James Bradley; Albert, Daniel H.

doi:10.1016/s1054-3589(08)61012-1

Cited by 48 publications

(30 citation statements)

References 393 publications

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“…Nuclei were then loaded with 4 M fura 2 and 0.05% pluronic F-127 (Calbiochem) for 45 min at 4°C. Nuclear suspension (ϳ2 ϫ 10 5 nuclei/ml) was incubated at 37°C and stimulated thereafter with C-PAF in the absence or presence (15 min before C-PAF) of preactivated PTX (20 g/ml; Calbiochem) or PAF receptor blockers CV 3988 and PCA 4248 (Biomol) (33).…”

Section: Calcium Signalingmentioning

confidence: 99%

Proinflammatory Gene Induction by Platelet-Activating Factor Mediated Via Its Cognate Nuclear Receptor

Marrache

Gobeil

Bernier

et al. 2002

The Journal of Immunology

115

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It has been postulated that intracellular binding sites for platelet-activating factor (PAF) contribute to proinflammatory responses to PAF. Isolated nuclei from porcine cerebral microvascular endothelial cells (PCECs) produced PAF-molecular species in response to H2O2. Using FACS analysis, we demonstrated the expression of PAF receptors on cell and nuclear surfaces of PCECs. Confocal microscopy studies performed on PCECs, Chinese hamster ovary cells stably overexpressing PAF receptors, and isolated nuclei from PCECs also showed a robust nuclear distribution of PAF receptors. Presence of PAF receptors at the cell nucleus was further revealed in brain endothelial cells by radioligand binding experiments, immunoblotting, and in situ in brain by immunoelectron microscopy. Stimulation of nuclei with methylcarbamate-PAF evoked a decrease in cAMP production and a pertussis toxin-sensitive rise in nuclear calcium, unlike observations in plasma membrane, which exhibited a pertussis toxin-insensitive elevation in inositol phosphates. Moreover, on isolated nuclei methylcarbamate-PAF evoked the expression of proinflammatory genes inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) and was associated with augmented extracellular signal-regulated kinase 1/2 phosphorylation and NF-κB binding to the DNA consensus sequence. COX-2 expression was prevented by mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 and NF-κB inhibitors. This study describes for the first time the nucleus as a putative organelle capable of generating PAF and expresses its receptor, which upon stimulation induces the expression of the proinflammatory gene COX-2.

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Section: Calcium Signalingmentioning

confidence: 99%

Proinflammatory Gene Induction by Platelet-Activating Factor Mediated Via Its Cognate Nuclear Receptor

Marrache

Gobeil

Bernier

et al. 2002

The Journal of Immunology

115

View full text Add to dashboard Cite

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“…(1984) demonstrated that the isolated kidney is able to produce substances such as histamine, serotonin and platelet-activating factor. The kidney tubules did not produce platelet-activating factor directly, but a precursor has been identified and the activity of the enzyme acetyltransferase has been shown in the glomeruli and in other kidney cells (Summers & Albert 1995). Platelet-activating factor is also involved in the vascular reactivity as demonstrated in the vascular escape and tachyphylaxis (Ferreira & Fonteles 1996).…”

Section: Effects Of Bn 52021 Web 2086 Und Indomethacin Onmentioning

confidence: 99%

The Effect of Bothrops Jararaca Venom on Rat Kidney After Short‐Term Exposure: Preliminary Results

Monteiro

Fonteles

1999

Pharmacology & Toxicology

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“…Activation of PAF-R leads to the activation of several signal-transduction pathways [15,16]. Studies on comparative quantification of PAF-R in organ\tissue are rare, probably because of the technical difficulty of differentiating membrane binding and membrane intercalation of a phospholipid [2,17]. The recent development of quantitative PCR and cloning of PAF-R cDNA from guinea-pig [18], human [19,20] and rat [21] tissues has greatly facilitated our understanding of PAF-R gene expression and regulation.…”

Section: Introductionmentioning

confidence: 99%

Regulation of platelet-activating factor receptor gene expression in vivo by endotoxin, platelet-activating factor and endogenous tumour necrosis factor

Wang

Tan

Chang

et al. 1997

Biochemical Journal

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A competitive PCR assay was developed to quantify platelet-activating factor (PAF) receptor (PAF-R) transcripts in rat tissues using a synthetic RNA as a competitor. We found PAF-R mRNA constitutively expressed in the eight organs tested, with the ileum containing the highest concentration [(3.49±0.15)×107 molecules/μg of RNA]. Significant but lower levels were also detected in the jejunum, spleen, lungs, kidneys, heart, stomach and liver. Furthermore we defined the regulatory role of inflammatory mediators in ileal PAF-R gene expression using a rat model of intestinal injury induced by PAF or lipopolysaccharide (LPS). Injection of LPS or low-dose PAF resulted in a marked increase in ileal PAF-R mRNA within 30 min. The up-regulation on PAF-R elicited by PAF was biphasic, peaking first at 90 min, then again at 6 h. In contrast, LPS elicited a weak monophasic response. The second phase of PAF-R mRNA increase after PAF administration was completely abolished by WEB 2170, a PAF antagonist, and partially inhibited by anti-tumour necrosis factor (TNF) antibody. These observations indicate the involvement of endogenous PAF and TNF in this event. In conclusion, we found: (a) preferential PAF-R expression in the ileum, suggesting a role for PAF in intestinal inflammation; (b) induction of PAF-R expression in vivo by its own agonist; (c) a complex regulation of PAR-R gene expression in vivoinvolving a network of various pro-inflammatory mediators.

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Platelet Activating Factor Antagonists

Cited by 48 publications

References 393 publications

Proinflammatory Gene Induction by Platelet-Activating Factor Mediated Via Its Cognate Nuclear Receptor

Proinflammatory Gene Induction by Platelet-Activating Factor Mediated Via Its Cognate Nuclear Receptor

The Effect of Bothrops Jararaca Venom on Rat Kidney After Short‐Term Exposure: Preliminary Results

Regulation of platelet-activating factor receptor gene expression in vivo by endotoxin, platelet-activating factor and endogenous tumour necrosis factor

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