Disease relevance of Ptafr

• Furthermore, the hypotension and intestinal injury was prevented by PAF receptor blockade [1].
• To determine whether PAF receptor (PAFR) expression is altered during excitotoxicity, changes in PAFR mRNA localization were compared with markers of neuronal apoptosis and reactive gliosis following systemic injection of kainic acid [2].
• The production of platelet-activating factor (PAF) and PAF-like phospholipids that also bind the PAF receptor are implicated in numerous pathological situations including bacterial endotoxemia and injury-induced oxidative damage [3].
• Pulmonary responses detected (i.e., eicosanoid production, leukocytic infiltration, Evan's blue extravasation, beta-glucuronidase release) were attenuated to varying degrees by treatment of rats in which pancreatitis was initiated with the PAF receptor antagonists (WEB2170 and BN52021) [4].
• With the use of this novel PAF receptor antagonist, the in vivo mediator role of PAF in the soluble immune complex-induced hypotension, extravasation, vascular lysosomal hydrolase secretion, and neutropenia in rats was determined [5].

Psychiatry related information on Ptafr

• Pretreatment of animals by intracerebroventricular injection with the intracellular platelet-activating factor receptor antagonist BN 50730 strongly attenuates kainic acid and electroconvulsive shock induction of prostaglandin G/H synthase-2 expression [6].

High impact information on Ptafr

• We found that PAF (control) and the oxidized phospholipids each induced release of arachidonic acid from the transfected cells, but had no effect on wildtype Chinese hamster ovary cells, which lack the PAF receptor [7].
• Using a Xenopus oocyte expression system, we obtained evidence for functional PAF receptor mRNA expression in rat brain [8].
• Moreover, the enhancement of excitatory synaptic transmission by carbamyl-PAF was blocked by a PAF receptor antagonist [9].
• The PAF receptor antagonist, L-652,731, blocked responses (O2-. production and enzyme release) of rat neutrophils stimulated with PAF but did not block responses triggered by immune complexes, formyl chemotactic peptide or opsonized zymosan particles [10].
• We tested the effect of PAF receptor antagonists, CV 3988 and SRI 63-441, on endotoxin-induced hemodynamic changes and lung vascular injury [11].

Chemical compound and disease context of Ptafr

• PAF-induced proteinuria was prevented by L-652,731, a specific PAF receptor antagonist, suggesting that PAF's effect on glomerular permeability to proteins is likely to be related to its biologic activity [12].
• Moreover, PGE1 did not inhibit the PAF-induced hypotension in vivo, indicating that PGE1 is not a PAF receptor antagonist [13].
• Thus, for the first time, the use of quantitative colocalization analysis software developed by us has reveal intrinsic details of the interaction of PAF anf PAF-R in conjunctivitis, findings not otherwise obtainable by using qualitative approaches alone [14].
• Platelet activating factor (PAF) involvement in endotoxin-induced hypotension in rats. Studies with PAF-receptor antagonist kadsurenone [15].
• Inhibition and reversal of endotoxin-, aggregated IgG- and paf-induced hypotension in the rat by SRI 63-072, a paf receptor antagonist [16].

Biological context of Ptafr

• Platelet activating factor receptor expression is associated with neuronal apoptosis in an in vivo model of excitotoxicity [2].
• Data from semi-quantitative RT-PCR, in situ hybridization, DNA fragmentation, cellular morphology analysis, and immunohistochemistry demonstrate that the localization of PAFR mRNA is altered during kainic acid-induced neurodegeneration [2].
• Here, we show that a mutant of PAFR (D289A), which does not couple to G proteins, was resistant to agonist-induced receptor phosphorylation [17].
• Blockade of neutrophil influx with platelet-activating factor receptor antagonists or cell adhesion molecule blockers prevented B(1) receptor up-regulation [18].
• Recombinant PAF-acetylhydrolase degrades PAF generated by NMDA-receptor activation; the hetrazepine BN50730 (an intracellular PAF receptor antagonist) also inhibits both NMDA-stimulated MAP kinases and neuronal cell death [19].

Anatomical context of Ptafr

• METHODS: The rat mesentery was superfused with the inhibitor of NO production NG-nitro-L-arginine methyl ester (L-NAME) either alone or in combination with WEB2086 (PAF receptor antagonist), SC41930 (LTB4 receptor antagonist), or quinacrine (PLA2 inhibitor) [20].
• Pretreatment with a platelet-activating factor receptor antagonist returned the LTC4-induced leukocyte rolling velocity to baseline levels [21].
• Suppression of lipopolysaccharide-induced nitric oxide synthase expression by platelet-activating factor receptor antagonists in the rat liver and cultured rat Kupffer cells [22].
• Treatment of experimental rats with WEB2170, a platelet-activating factor receptor antagonist, attenuated the hepatic injury and inflammation, as evidenced by decreases in plasma ALT and in hepatocyte necrosis and neutrophil infiltration [23].
• These results suggest predominant presence of PAF receptor in microglia [24].

Associations of Ptafr with chemical compounds

• Previous injection of the specific platelet-activating factor receptor antagonists, BN 52021 or BN 50730, was also unable to restore a normal marker excretion profile after administration of trinitrobenzene sulfonic acid [25].
• Platelet activating factor (PAF) is a potent phospholipid mediator which elicits a diverse array of biological actions by interacting with G protein-coupled PAF receptors (PAFR) [26].
• Therefore, using 16 rats, we studied the effects of the platelet activating factor receptor blockers BN 52021 (10 mg/kg, n = 4 or 30 mg/kg, n = 2) and WEB 2086 (5 mg/kg, n = 6) on global cerebral blood flow and the cerebral metabolic rate for oxygen and compared them with the effect of indomethacin (10 mg/kg, n = 4) [27].
• This enhancement was blocked by three structurally unrelated specific PAF receptor antagonists BN 52021, WEB 2170, and CV 3988 [28].
• Although PAF stimulated 10-fold increases in inositol phosphate accumulation in rPAFR transfectants, it had no effects on inositol phosphate accumulation in amphipathic helix mutant PAFR transfectants [29].

Regulatory relationships of Ptafr

• 2. Pre-treatment with the PAF receptor antagonist WEB 2086 inhibited des-Arg(9)-BK-induced oedema in IL-1 beta-treated paws, while the LTB(4) receptor antagonist CP105696 had no effect [30].
• The PAF receptor antagonist WEB 2170 almost completely blocked the ATS and RS induced MCP-1 mRNA levels [31].

Other interactions of Ptafr

• Pretreatment with intravenous administration of BM 13505 (1 mg kg-1), a TxA2 receptor antagonist, OKY-046 (10 mg kg-1), a thromboxane synthase inhibitor or the specific PAF receptor antagonist, WEB 2086 (1 mg kg-1) or BN 52021 (10 mg kg-1) markedly suppressed ST segment elevation in response to ET-1 [32].
• Rats pretreated with a specific PAF receptor antagonist exhibited suppression of the increase in plasma TNF-alpha and CINC levels, as well as the priming of peripheral neutrophils for superoxide production after reperfusion when compared with animals pretreated with physiological saline [33].
• The possible dependence of CINC-1 induction on the autocrine generation of lipid mediators was ruled out by a set of experiments including the use of the PAF receptor antagonist BB823, and the analysis of the effect of free arachidonate and leukotriene B4 on CINC-1 induction [34].
• Inhibitory effect of platelet-activating factor (PAF) on luteinizing hormone-releasing hormone and somatostatin release from rat median eminence in vitro correlated with the characterization of specific PAF receptor sites in rat hypothalamus [35].
• RESULTS: Pretreatment with lexipafant, a potent PAF receptor antagonist, significantly reduced the pancreatitis-induced increase in pancreatic endothelial barrier dysfunction, pancreatic leukocyte recruitment and serum levels of IL-1 beta, although a difference persisted between animals with sham operation and pancreatitis [36].

Analytical, diagnostic and therapeutic context of Ptafr

• In situ hybridization revealed that the PAF receptor mRNA is expressed intensely in microglia and moderately in neurons [24].
• Northern blot analysis revealed that PAF receptor mRNA is the most abundant in microglia [24].
• Additionally, pancreatic microvascular endothelial cells were isolated and examined for the PAF receptor using immunohistochemistry, reverse transcription-polymerase chain reaction, and intracellular calcium responses to PAF exposure [37].
• The data demonstrate a beneficial effect of the platelet activating factor receptor antagonist in this animal model of proliferative glomerulonephritis which suggests that platelet activating factor might play an important role in the mediation of this disease [38].
• 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 [39].

References