Disease relevance of Ptafr

• Platelet-activating factor induced a pertussis toxin-sensitive [Ca(2+)](i) transient in two-cell embryos that did not occur in platelet-activating factor-receptor null (Pafr-/-) genotype embryos [1].
• beta-Arrestin 1 participates in platelet-activating factor receptor-mediated endocytosis of Streptococcus pneumoniae [2].
• Through observations of bone mineral density and histomorphometric parameters, it was found that bone resorption was markedly attenuated in PAF receptor-deficient mice, indicating that PAF links estrogen depletion and osteoporosis in vivo [3].
• Conversely, mice carrying a targeted disruption of the PAFR gene experienced significantly less acid-induced injury, edema, and respiratory failure [4].
• Overexpression of the PAFR gene in transgenic mice enhanced lung injury, pulmonary edema, and deterioration of gas exchange caused by HCl aspiration [4].

Psychiatry related information on Ptafr

• Taken together, these results demonstrate that PMS777 possesses dual activities for PAF receptor antagonism and AChE inhibition, suggesting that this compound may be a promising lead compound for further investigation related to the treatment for Alzheimer's disease [5].
• These results suggest that BN-50730, a PAF receptor antagonist, produced retrograde amnesia and physostigmine attenuated BN-50730-induced amnesia possibly through increased concentration of cerebral acetylcholine and a consequent increase in PAF release [6].

High impact information on Ptafr

• The levels of PAF production and PAFR mRNA expression in the spinal cord (SC) correlated with the EAE symptoms [7].
• To investigate the role of platelet-activating factor (PAF) in this disease, PAF receptor (PAFR) KO (PAFR-KO) and wild-type (WT) mice, on a C57BL/6 genetic background, were immunized with myelin oligodendrocyte glycoprotein 35-55 [7].
• In addition to the well-known role of PAF as a proinflammatory lipid mediator, we propose that the PAF receptor senses cellular damage through the recognition of PAF and/or PAF-like molecules, such as oxidized phosphatidylcholine, which activates cytokine transcription and induces systemic immune suppression [8].
• Treatment with the neurokinin (NK)(1) and NK(3) receptor antagonists attenuated the responses, whereas NK(2), calcitonin gene-related peptide, or platelet-activating factor receptor antagonists had no effect [9].
• In this model the angiogenesis induced by TNF-alpha was shown to be inhibited by WEB 2170, a specific PAF receptor antagonist [10].

Chemical compound and disease context of Ptafr

• Analysis of mRNA from multiple sclerosis lesions revealed increased amounts of transcripts for several genes encoding molecules traditionally associated with allergic responses, including prostaglandin D synthase, histamine receptor type 1 (H1R), platelet activating factor receptor, Ig Fc epsilon receptor 1 (Fc epsilon RI), and tryptase [11].
• Treatment with the PAF receptor antagonist L659,989 for four weeks, starting at 12 weeks of age, significantly reduced acute glomerular infiltration and proliferation, and prevented chronic glomerular histological changes; proteinuria and serum creatinine levels were also significantly reduced in treated mice [12].
• A diet supplemented with flaxseed, rich in alpha-linolenic acid and plant lignans (the latter, potent platelet-activating factor receptor antagonists), was tested in a murine model of lupus nephritis [13].
• The PAF antagonists, WEB 2170 and WEB 2086, provided the best dose-dependent protection against PAF toxicity, followed by dexamethasone, by the COX/LOX synthetase inhibitor X 86 (a BW 755 C-analogue) and by the PAF receptor antagonist BN 52021 [14].
• These results suggest that PAF receptor antagonists alone and in combination with tacrolimus/sodium valproate could be used in the treatment of cerebral ischemia reperfusion injuries however, their use following peripheral nerve injuries could be detrimental [15].

Biological context of Ptafr

• Pneumococci colocalized with PAFr on endothelial cells and PAFr-/- mice showed a substantially impaired ability to support bacterial translocation, particularly from blood to brain [2].
• Furthermore, our findings provide new insights regarding the role of PAF in the morphogenesis of dermal tissues as well as the mitogenic activity of PAF and PAFR in vivo [16].
• Platelet-activating factor receptor and innate immunity: uptake of gram-positive bacterial cell wall into host cells and cell-specific pathophysiology [17].
• Molecular studies demonstrate the differential expression of platelet-activating factor receptor and TLR-4 in uterine and cervical tissue throughout gestation [18].
• Thus, in S. venezuelensis-infected PAFR(-/-) mice, decreased intestinal inflammation is associated with enhanced worm survival but decreased fecundity [19].

Anatomical context of Ptafr

• Fewer Pafr-/- mouse zygotes developed to the blastocyst stage in vitro compared with Pafr+/+ zygotes (P<0.02), those that developed to blastocysts had fewer cells (P<0.001) and more cells with fragmented nuclei (P<0.001) [1].
• This study was designed to characterize PAF receptor (PAF-R) expression and its specific contribution to the modifications of adherens junctions in mouse endothelial cells [20].
• PAF receptor stimulation prolonged the survival of osteoclasts in vitro [3].
• Osteoclasts, but not osteoblasts, expressed the functional PAF receptor [3].
• Degradation of platelet-activating factor (PAF) was examined by incubating PAF with macrophages from PAF receptor-deficient mice [21].

Associations of Ptafr with chemical compounds

• Thus, PAFr shepherds phosphorylcholine-containing bacterial components such as the cell wall into host cells from where the response ranges from quiescence to severe pathophysiology [17].
• Intravascular choline-containing cell walls bound to endothelial cells and caused rapid lethality in wild-type, Tlr2(-/-), and Nod2(-/-) mice but not in Pafr(-/-) mice [17].
• Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice [22].
• When C3H/HeN macrophages were treated with bacterial lipopolysaccharide (LPS) or synthetic lipid A, the PAFR gene expression was induced [23].
• Furthermore, the biological activity of oxidized MVs is inhibited by platelet-activating factor receptor antagonists, which have been shown to inhibit the action of POVPC [24].

Regulatory relationships of Ptafr

• In addition, release of PAF acetylhydrolase from macrophages was enhanced when wild-type macrophages were stimulated with PAF but not from macrophages of PAF receptor-deficient mice [21].
• Inhibitors of platelet-activating factor receptor (PAFR) blocked LTA- or Pam3CSK4-induced production of NO but not TNF-alpha [25].
• Jet fuel-induced PGE2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists [26].
• Our findings suggest that the NMDA receptor/NO signaling pathway might contribute to the pathological mechanism of cell death triggered via PAF receptor activation [27].
• CONCLUSION: The dithiolane analogs are a new synthetic chemical class of iNOS expression regulators with dual biologic functions: inhibiting iNOS induction and blocking PAF-receptor [28].

Other interactions of Ptafr

• We conclude that the association of beta-arrestin with the PAFr contributes to successful translocation of pneumococci [2].
• We demonstrated that PAF-R was expressed in mouse endothelial cells and was functionally active in stimulating p42/p44 MAPK and phosphatidylinositol 3-kinase (PtdIns3'-kinase)/Akt activities [20].
• 4 Pretreatment with PAFR antagonist UK-74,505 (1 mg kg(-1)) markedly prevented tissue injury, as assessed by the increase in vascular permeability, neutrophil accumulation, hemorrhage and TNF-alpha concentrations in the intestine and lungs [29].
• Interestingly, the reperfusion-associated increases in tissue concentrations of IL-10 were significantly greater in PAFR(-/-) than wild-type mice [29].
• This study confirms the presence of the G protein-linked PAF receptor in the 2-cell embryo and describes for the first time its normal pattern of expression during early development [30].

Analytical, diagnostic and therapeutic context of Ptafr

• Absence of platelet-activating factor receptor protects mice from osteoporosis following ovariectomy [3].
• Consistently, in organ cultures, bone resorption was significantly suppressed by a PAF receptor antagonist treatment or genetic PAF receptor deficiency [3].
• Immunohistochemistry studies demonstrate the presence of the platelet-activating factor receptor in both endometrial glands and smooth muscle in uterine tissues [18].
• Northern blot analysis showed a high expression of the PAFR message in peritoneal macrophages [23].
• 3 After reperfusion of the ischemic SMA, PAFR(-/-) mice had little tissue or systemic inflammation and lethality was delayed, but not prevented, in these mice [29].

References