Platelet-Activating Factor (PAF) Receptor in Brain and Signal Transduction in Neurons

1991 ◽  
pp. 309-315
Author(s):  
Tian-Li Yue ◽  
Paul G. Lysko ◽  
Giora Feuerstein
Keyword(s):  
Signal Transduction ◽  
Platelet Activating Factor ◽  
Paf Receptor

scholarly journals Platelet-activating factor: receptors and signal transduction

1993 ◽  
Vol 292 (3) ◽  
pp. 617-629 ◽  
Author(s):  
W Chao ◽  
M S Olson
Keyword(s):  
Signal Transduction ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Molecular Genetic ◽  
Platelet Activating Factor ◽  
Cellular Adhesion ◽  
Cellular Adhesion Molecules ◽  
The Past ◽  
Signalling Molecule ◽  
Paf Receptor

During the past two decades, studies describing the chemistry and biology of PAF have been extensive. This potent phosphoacylglycerol exhibits a wide variety of physiological and pathophysiological effects in various cells and tissues. PAF acts, through specific receptors and a variety of signal transduction systems, to elicit diverse biochemical responses. Several important future directions can be enumerated for the characterization of PAF receptors and their attendant signalling mechanisms. The recent cloning and sequence analysis of the gene for the PAF receptor will allow a number of important experimental approaches for characterizing the structure and analysing the function of the various domains of the receptor. Using molecular genetic and immunological technologies, questions relating to whether there is receptor heterogeneity, the precise mechanism(s) for the regulation of the PAF receptor, and the molecular details of the signalling mechanisms in which the PAF receptor is involved can be explored. Another area of major significance is the examination of the relationship between the signalling response(s) evoked by PAF binding to its receptor and signalling mechanisms activated by a myriad of other mediators, cytokines and growth factors. A very exciting recent development in which PAF receptors undoubtedly play a role is in the regulation of the function of various cellular adhesion molecules. Finally, there remain many incompletely characterized physiological and pathophysiological situations in which PAF and its receptor play a crucial signalling role. Our laboratory has been active in the elucidation of several tissue responses in which PAF exhibits major autocoid signalling responses, e.g. hepatic injury and inflammation, acute and chronic pancreatitis, and cerebral stimulation and/or trauma. As new experimental strategies are developed for characterizing the fine structure of the molecular mechanisms involved in tissue injury and inflammation, the essential role of PAF as a primary signalling molecule will be affirmed. Doubtless the next 20 years of experimental activity will be even more interesting and productive than the past two decades.

scholarly journals Lack of Platelet-Activating Factor Receptor Attenuates Experimental Food Allergy but Not Its Metabolic Alterations regarding Adipokine Levels

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Nathália Vieira Batista ◽  
Roberta Cristelli Fonseca ◽  
Denise Perez ◽  
Rafaela Vaz Sousa Pereira ◽  
Juliana de Lima Alves ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Food Allergy ◽  
Inflammatory Process ◽  
Platelet Activating Factor ◽  
Oral Challenge ◽  
Tissue Loss ◽  
Lack Of Information ◽  
Paf Receptor ◽  
Rolling Leukocytes

Platelet-activating factor (PAF) is known to be an important mediator of anaphylaxis. However, there is a lack of information in the literature about the role of PAF in food allergy. The aim of this work was to elucidate the participation of PAF during food allergy development and the consequent adipose tissue inflammation along with its alterations. Our data demonstrated that, both before oral challenge and after 7 days receiving ovalbumin (OVA) diet, OVA-sensitized mice lacking the PAF receptor (PAFR) showed a decreased level of anti-OVA IgE associated with attenuated allergic markers in comparison to wild type (WT) mice. Moreover, there was less body weight and adipose tissue loss in PAFR-deficient mice. However, some features of inflamed adipose tissue presented by sensitized PAFR-deficient and WT mice after oral challenge were similar, such as a higher rate of rolling leukocytes in this tissue and lower circulating levels of adipokines (resistin and adiponectin) in comparison to nonsensitized mice. Therefore, PAF signaling through PAFR is important for the allergic response to OVA but not for the adipokine alterations caused by this inflammatory process. Our work clarifies some effects of PAF during food allergy along with its role on the metabolic consequences of this inflammatory process.

Mechanisms contributing to gastric motility changes induced by PAF-acether and endotoxin in rats

1989 ◽  
Vol 256 (2) ◽  
pp. G275-G282
Author(s):  
J. V. Esplugues ◽  
B. J. Whittle
Keyword(s):  
Gastric Motility ◽  
Platelet Activating Factor ◽  
Mucosal Damage ◽  
Serotonin Release ◽  
Initial Increase ◽  
Intragastric Pressure ◽  
Paf Receptor ◽  
Endogenous Release ◽  
Gastric Contractions

Platelet-activating factor (PAF) may be involved in the pathophysiology of gastrointestinal damage and motility changes. The effects of PAF in inducing gastric contractions in vivo have now been determined in pentobarbital sodium-anesthetized rats. Local intra-arterial infusion of PAF (5-50 ng.kg-1.min-1 for 10 min) induced a maintained rise in intragastric pressure followed by a further postinfusion increase. Inhibitors of eicosanoid biosynthesis had no effect on these gastric motility changes. However, pretreatment with cimetidine or methysergide decreased by 50% the initial increase in intragastric pressure, whereas mepyramine, adrenergic alpha- and beta-receptor blockade, atropine, hexamethonium, or vagotomy had no effect. During the local infusion of tetrodotoxin, the initial increase in intragastric pressure was not maintained, and the postinfusion increase was abolished. With these inhibitors and antagonists, there was no consistent correlation between the extent of PAF-induced mucosal damage and increase in intragastric pressure. Tetrodotoxin had no effect on the changes in intragastric pressure induced by the thromboxane mimetic U-46619. Administration of Escherichia coli and Salmonella typhosa endotoxin (50 mg/kg iv) also increased intragastric pressure, which peaked after 10 min and slowly declined thereafter. These effects were inhibited by the specific PAF-receptor antagonist L652,731, suggesting that the endogenous release of PAF may contribute to the endotoxin-induced increases in gastric motility. The present study suggests that PAF initially acts directly on smooth muscle and through histamine and serotonin release with a secondary motility response due to activation of nonadrenergic noncholinergic, neuronal activity.

Oxidized low-density lipoprotein and peroxisome-proliferator-activated receptor α down-regulate platelet-activating-factor receptor expression in human macrophages

2001 ◽  
Vol 354 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Delphine HOURTON ◽  
Philippe DELERIVE ◽  
Jana STANKOVA ◽  
Bart STAELS ◽  
M. John CHAPMAN ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Platelet Activating Factor ◽  
Density Lipoprotein ◽  
Receptor Expression ◽  
Peroxisome Proliferator ◽  
Low Density ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Mrna ◽  
Paf Receptor ◽  
Pparα Agonist

Regulation of the expression of platelet-activating factor (PAF) receptor by atherogenic lipoproteins might contribute to atherogenesis. We show that progressive oxidation of low-density lipoprotein (LDL) gradually inhibits PAF receptor expression on the macrophage cell surface. We tested the effect of oxidized LDL (oxLDL) on PAF receptor expression in human monocytes that do not contain peroxisome-proliferator-activated receptor γ (PPARγ), a nuclear receptor activated by oxLDL. OxLDL decreased by 50% (P ⩽0.001) and by 29% (P⩽0.05) the binding of PAF and the expression of PAF receptor mRNA respectively. Next we demonstrated that progressive oxidation of LDLs significantly activated PPARα-dependent transcription in transfected mouse aortic endothelial cells. Finally we demonstrated, in mature macrophages, that fenofibrate (20µM), a specific PPARα agonist, but not the specific PPARγ agonist BRL49653 (20nM), significantly decreased both PAF binding and PAF receptor mRNA expression, by 65% and 40% (P⩽0.001) respectively. Additionally, another PPARα agonist, Wy14,643, decreased PAF receptor promoter activity by 70% (P⩽0.05) in transfected THP-1 cells, suggesting the involvement of the proximal promoter region (-980 to -500) containing a series of four nuclear factor (NF)-κB motifs. Thus PPARα might be involved in the down-regulation of PAF receptor gene expression by oxLDLs in human monocytes/macrophages. The oxidation of one or more lipid components of LDLs might result in the formation of natural activators of PPARα. It is hypothesized that such activators might modulate inflammation and apoptosis upon atherogenesis by decreasing the expression of PAF receptor.

scholarly journals Platelet-activating factor (PAF) receptor expression is associated with histopathological stage and grade and patients’ survival in gastric adenocarcinoma

Neoplasma ◽  
2014 ◽  
Vol 61 (03) ◽  
pp. 309-317 ◽  
Author(s):  
C. GIAGINIS,E. KOUROU ◽  
A. GIAGINI ◽  
N. GOUTAS ◽  
E. PATSOURIS ◽  
G. KOURAKLIS ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Platelet Activating Factor ◽  
Receptor Expression ◽  
Paf Receptor

scholarly journals Interleukin-1-induced leukocyte extravasation across rat mesenteric microvessels is mediated by platelet-activating factor

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2553-2558 ◽  
Author(s):  
S Nourshargh ◽  
SW Larkin ◽  
A Das ◽  
TJ Williams
Keyword(s):  
Vessel Wall ◽  
Interleukin 1 ◽  
Platelet Activating Factor ◽  
Micron Diameter ◽  
Paf Receptor ◽  
Leukocyte Extravasation ◽  
Mesenteric Microvessels ◽  
Adherent Leukocytes

Although our understanding of the molecular interactions that mediate the adhesion of leukocytes to venular endothelial cells has greatly expanded, very little is known about the mechanisms that mediate the passage of leukocytes across the vessel wall in vivo. The aim of the present study was to investigate the role of endogenously formed platelet-activating factor (PAF) in the process of leukocyte extravasation induced by interleukin-1 (IL-1). To determine at which stage of emigration PAF was involved, we studied the behavior of leukocytes within rat mesenteric microvessels by intravital microscopy. Rats were injected intraperitoneally with saline, recombinant rat IL-1 beta (IL-1 beta), or the peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) 4 hours before the exteriorization of the mesenteric tissue. In animals treated with IL-1 beta there was a significant increase in the number of rolling and adherent leukocytes within venules (20- to 40-micron diameter) and in the number of extravasated leukocytes in the tissue. Pretreatment of rats with the PAF receptor antagonist UK-74,505 had no effect on the leukocyte responses of rolling and adhesion, but significantly inhibited the migration of the leukocytes across the vessel wall induced by IL-1 beta (76% inhibition). A structurally unrelated PAF antagonist, WEB-2170, produced the same effect (64% inhibition). However, in contrast, UK-74,505 had no effect on the leukocyte extravasation induced by FMLP, indicating selectivity for the response elicited by certain mediators. These results provide the first line of direct evidence for the involvement of endogenously formed PAF in the process of leukocyte extravasation induced by IL-1 in vivo.

Platelet-activating factor antagonists increase vascular reactivity in perfused rat lungs

1988 ◽  
Vol 65 (5) ◽  
pp. 1921-1928 ◽  
Author(s):  
J. Haynes ◽  
S. W. Chang ◽  
K. G. Morris ◽  
N. F. Voelkel
Keyword(s):  
Pulmonary Circulation ◽  
Vascular Reactivity ◽  
Platelet Activating Factor ◽  
Base Line ◽  
Ang Ii ◽  
Rat Lungs ◽  
Hypoxic Vasoconstriction ◽  
Paf Receptor ◽  
Blood Elements

Platelet-activating factor (PAF) administered to the pulmonary circulation in low dose (nanogram) has vasodilatory properties. Therefore, we investigated whether endogenous PAF plays a role in the control of tone in the pulmonary circulation. The PAF receptor antagonists, SRI 63-441 (2.6 X 10(-4) M) and L659,989 (1 X 10(-5) M), were the major investigative tools. In isolated perfused rat lungs, both agents caused a persistent increase in base-line perfusion pressure (Ppa), potentiated angiotensin II (ANG II) vasoconstriction, and potentiated hypoxic vasoconstriction (HPV). This potentiation of ANG II and HPV was found to be independent of circulating blood elements. Vasodilation in the presence of PAF blockade was also impaired. The combination of cyclooxygenase inhibition and PAF receptor blockade had an additive effect on ANG II vasoconstriction but did not cause more potentiation of HPV than achieved with PAF antagonism alone. In vivo, SRI 63-441 (10 mg/kg) caused only a transient increase in base-line Ppa without altering ANG II and hypoxic vasoconstriction. These findings support a vasodilatory role for endogenous PAF in the pulmonary circulation.

Exogenous xanthine promotes neutrophil adherence to cultured endothelial cells

1997 ◽  
Vol 273 (2) ◽  
pp. G342-G347
Author(s):  
H. Ichikawa ◽  
R. E. Wolf ◽  
T. Y. Aw ◽  
N. Ohno ◽  
L. Coe ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Injury ◽  
Umbilical Vein ◽  
Platelet Activating Factor ◽  
Adhesion Assay ◽  
Neutrophil Adherence ◽  
Paf Receptor ◽  
Umbilical Vein Endothelial Cells ◽  
Adhesive Effect ◽  
Paf Receptor Antagonist

Oxidants generated by endothelial xanthine oxidase (XO) can help trigger free radical-mediated tissue injury. An important event in oxidant-mediated tissue injury is neutrophil-endothelial adhesion. Although activation of endothelial XO increases adhesion, little is known about xanthine in the adhesive effect of XO. This study examined administered xanthine on the adhesion of neutrophils. Endothelial [human umbilical vein endothelial cells (HUVEC)] monolayers were exposed to xanthine (15 min), and neutrophils were allowed to adhere to HUVEC in an adhesion assay. Adhesion was dose dependently increased by xanthine (3-100 microM). Either catalase (1,000 U/ml), oxypurinol (XO inhibitor; 100 microM), or platelet-activating factor (PAF) receptor antagonist (WEB 2086; 10 microM) reduced neutrophil adhesion. Superoxide dismutase (1,000 U/ml) had no effect. Pretreatment of HUVEC with 50 microM tungsten also blocked xanthine-induced adherence. Adhesion was also inhibited by preincubation with 100 U/ml heparin. Finally, anti-P-selectin antibody (PB1.3; 20 micrograms/ml) attenuated adhesion. Our results indicate that xanthine may promote neutrophil-endothelial adhesion via a hydrogen peroxide- and PAF-mediated P-selectin expression.

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