Disease relevance of L 652731

• When L-652,731 was added to the antibody employed in the reversed passive Arthus reaction, the injury resulting from immune complex-induced vasculitis was significantly attenuated [1].
• The same L-652,731-dosing regimen inhibited immune complex-stimulated hypotension (87%), extravasation (77%), and vascular lysosomal hydrolase release (31%) [2].
• L-652,731 when orally administered to rats (20 mg/kg, 1.5 hr before PAF infusion) inhibited PAF-induced hypotension (69%), extravasation (76%), vascular lysosomal hydrolase release (79%), and neutropenia (73%) [2].
• To evaluate if PAF has a major role in promoting glomerular inflammatory reaction and fibrin deposition, we studied the effect of a molecule, L-652,731, which blocks the PAF receptor, on the evolution of an experimental model of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) [3].
• 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 [4].

High impact information on L 652731

• With this model, we demonstrated that the effects of neutrophil reconstitution are substantially diminished if the cells are pretreated with L-652,731 and then washed [1].
• The antagonists WEB 2086 and L-652,731 had no effect on neutrophil migration across resting EC induced by formylmethionyl-leucyl-phenylalanine (FMLP) [5].
• The PAF induction of the acetyltransferase was less sensitive to inhibition by the specific PAF receptor antagonist L-652,731 than was PAF-induced degranulation [6].
• Intratracheal instillation of anti-IL-1 beta plus L-652,731 resulted in reduction in lung vascular permeability and retarded net pulmonary neutrophil recruitment [7].
• In contrast, L-652,731 had little effect on MDP-induced IL-1 synthesis in the absence of exogenous paf [8].

Chemical compound and disease context of L 652731

• Intravenous infusion of 1 mumol L-652,731 results in almost 100% inhibition of hypotension induced by PAF but not that induced by isoproterenol, histamine, bradykinin, or acetylcholine [2].
• Effects of L-652,731, a platelet-activating factor (PAF) receptor antagonist, on PAF- and complement-induced pulmonary hypertension in sheep [9].
• Effect of the PAF antagonists, CV-3988 and L-652,731 on the pulmonary and hematological responses to guinea pig anaphylaxis [10].

Biological context of L 652731

• L-652,731 is orally active; it inhibits PAF-induced rat cutaneous vascular permeability with an ED50 of 30 mg/kg orally [11].
• The most potent PAF antagonist in this group of compounds is trans-2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran (L-652,731, 14) with an IC50 of 0.02 microM [12].
• Platelet aggregation induced by the thrombin-like enzymes could not be inhibited by PAF antagonists-BN 52021, kadsurenone or L-652,731 [13].
• Scatchard analysis of the binding data indicated that no significant change in the dissociation constant (Kd) and maximum number of binding sites (Bmax) occurred after preincubation of platelet membrane with L 652731, whereas a reduction of Bmax was observed when PAF and BN 52021 were measured [14].
• In addition, L-652,731 completely restored macrophage phagocytosis, partially improved macrophage killing and significantly inhibited leukopenia [15].

Anatomical context of L 652731

• When the paf receptor antagonist, L-652,731 was added to monocytes, it prevented the enhancement of IL-1 activity induced by exogenous paf [8].
• 5. The potencies of L-652,731 and BN 52021 were also markedly less (2 log units) for the macrophage receptors than for platelet or PMNL receptors and BN 52021 was more potent than L-652,731 in the macrophages [16].
• 1. The effects of the platelet activating factor (Paf) antagonists alprazolam, BN 52021, kadsurenone, L 652,731 and SRI 63119 have been studied on Paf-induced chemiluminescence (CL) of guinea-pig, C. parvum-activated peritoneal macrophages in vitro [17].
• When membranes were extensively washed, full recovery of specific [3H]PAF binding was attained with L 652731 and partial recoveries (60%, 55% and 30%) were reached with BN 52021, WEB 2086 and PAF, respectively; no recovery was seen with the dioxolanes BN 52111 and BN 52115 [14].
• The addition of L-652,731 and L-653,150, two synthetic PAF-specific receptor antagonists, to 72 hour cultures of phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear leukocytes (PBML) caused a dose-dependent inhibition of (3H)-thymidine incorporation into T-cells (IC50: 25 microM and 3.2 microM, respectively) [18].

Associations of L 652731 with other chemical compounds

• Platelet-activating factor (PAF) mediation of rat anaphylactic responses to soluble immune complexes. Studies with PAF receptor antagonist L-652,731 [2].
• Significant inhibitory results of L-652,731 suggest that PAF may be partially involved in cutaneous vascular permeability induced by histamine and bradykinin [11].
• 3. Several PAF antagonists, such as CV-3988, L-652,731 and Y-24,180 inhibited the histamine- and thrombin-induced neutrophil adherence in a concentration-dependent manner [19].
• The LTB4 antagonist U-75,302 10(-5) M, and the PAF antagonist L 652,731 10(-5) M in chambers containing LTB4 and PAF-acether respectively blocked significantly the influx of PMNs and eosinophils compared to vehicle (p less than 0.01) [20].

Gene context of L 652731

• Subplantar co-injection of PAF antagonist, BN 52021 or L 652731, with cardiotoxin had no effect on paw oedema, whereas superoxide dismutase/catalase reduced this oedematous response [21].
• Inhibition of neutrophil and eosinophil chemotactic responses to PAF by the PAF-antagonists WEB-2086, L-652,731, and SRI-63441 [22].
• Under the same conditions L-652,731 at the concentration of 5 x 10(-6) mol/litre inhibited (P less than .01) the eosinophil chemotactic response to 10(-8) and 10(-9) mol PAF per litre [22].
• 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 [9].
• PAF receptor antagonists (L-652,731, WEB2086, and FR900452) at up to 10 nmol per tube had no affect on the SPRIA [23].

Analytical, diagnostic and therapeutic context of L 652731

• In a reversed passive Arthus reaction, intradermal injection of L-652731 together with antibody resulted in a significant inhibition of the oedema formation measured for 2 hr after i.v. antigen challenge [24].
• The topical administration of L-652,731, (two doses of 100 micrograms as a 1% suspension), elicited a slight, but significant blockade of 23% [25].
• An intravenous injection of L-652,731, 0.3 mg/kg, followed by an infusion at 16 micrograms.kg-1. min-1 prevented the endotoxin-elicited reduction in GFR, RPF, and FF [26].

References