Disease relevance of PAFR

• PAF synthesis by fetal pulmonary vascular smooth muscle cells (PVSMC) is high in hypoxia, but how oxygen tension affects PAF receptor (PAF-r) binding in PVSMC is not known [1].
• We investigated whether platelet-activating factor (PAF) mediates endotoxin-induced systemic and pulmonary vascular derangements by studying the effects of a selective PAF receptor antagonist, SRI 63-441, during endotoxemia in sheep [2].
• Infusion of BN 52021 (20 mg/kg), a PAF receptor antagonist, before rechallenging the same sheep with heparin and then protamine did not reduce the level of peak pulmonary hypertension or the degree of hypoxemia and leukopenia [3].
• Mechanisms of glomerular injury in experimental immune nephritis. II. Effect of a platelet activating factor receptor antagonist in an autologous nephritis model [4].
• The role of Platelet Activating Factor (PAF) in experimental immune glomerulonephritis was assessed by administering the specific PAF receptor antagonist CV-3988 to inbred LEW rats with the Accelerated Autologous Nephrotoxic Serum Nephritis (AA-NTSN) [4].

High impact information on PAFR

• Oxygen-dependent PAF receptor binding and intracellular signaling in ovine fetal pulmonary vascular smooth muscle [1].
• Western analysis of endometrial tissue showed marked upregulation of PAF receptor protein expression from day 14 of the cycle, and immunolocalization studies showed that the receptor expression was predominantly around the endometrial glands [5].
• Endometrial tissue PAF receptor mRNA expression was induced (P < 0.01) by estradiol and progesterone treatment of animals, and transcripts were present between days 10 and 16 of the estrous cycle [5].
• We speculate that decreased PAF receptor binding immediately after birth will facilitate the fall in pulmonary vascular resistance in the immediate newborn period [6].
• We determined PAF receptor binding in lung membranes of four groups of perinatal lambs [6].

Biological context of PAFR

• PAF receptor gene measured by RT-PCR showed a significant downregulation of PAF receptor gene mRNA in lungs of lambs <1 day old, suggesting a transcriptional regulation of PAF receptor gene expression in the immediate newborn period [6].

Anatomical context of PAFR

• We conclude that the use of a specific PAF receptor antagonist, L-659,989, immediately before controlled coronary reflow attenuated the activation of platelets and neutrophils that occurred during reperfusion [7].
• Utilizing an intact sheep model that involved a 90-min occlusion of the mid-left anterior descending coronary artery followed by 6 hr of reperfusion, a study group that received a specific PAF receptor antagonist (L-659,989, 5 mg/kg) 10 min before reperfusion was compared to a control group that received a saline placebo (n = 8 in each group) [7].

Associations of PAFR with chemical compounds

• We investigated the effects of PAF infusions in unanesthetized sheep and the effects of the PAF receptor antagonist L-652,731 [trans-2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran] on the hematologic, hemodynamic and biochemical alterations produced by infusions of both ZAP and PAF [8].
• Treatment with CV-3988, a selective PAF receptor antagonist, but not with meclofenamate, atropine, or diphenhydramine and cimetidine blocked the response to PAF infusion and did not affect baseline tone [9].
• To test the hypothesis that PAF partially mediates endotoxin-induced lung dysfunction, we studied the effects of two structurally dissimilar PAF receptor antagonists (SRI 63-441 and WEB 2086) on endotoxin-induced lung dysfunction in chronically instrumented awake sheep [10].

Analytical, diagnostic and therapeutic context of PAFR

• The hypothesis of the present study is that PAF is central in the pathophysiology of myocardial reperfusion and that specific PAF receptor antagonism may reduce myocardial reperfusion injury [7].

References