title: Effect of Y-24180, an antagonist at platelet-activating factor (PAF) receptors, on IgE-mediated cutaneous reactions in mice.
abstract: OBJECTIVE
  We examined the effect of Y-24180, a potent platelet-activating factor (PAF) antagonist, on IgE-mediated cutaneous reactions in mice.
  
  
  METHODS
  Female BALB/c mice were used.
  
  
  METHODS
  Drugs were orally administered 1 h before a dinitrofluorobenzene (DNFB) challenge or 1 h before and 12 h after the challenge.
  
  
  METHODS
  Biphasic increase in ear thickness, with peak responses at 1 h (immediate phase reaction, IPR) and 24 h (late phase reaction, LPR) after the DNFB challenge, were induced in mice which had been passively sensitized with monoclonal anti-dinitrophenyl IgE antibody 24 h before the DNFB challenge. Ear thickness was measured with a dial thickness gauge.
  
  
  RESULTS
  Y-24180, WEB2086, ketotifen, and suplatast suppressed the IPR. Y-24180 also suppressed the LPR when administered once at 10 mg/kg or twice at 1 to 10 mg/kg. WEB2086 suppressed the LPR only when administered twice. However, ketotifen and suplatast did not suppress the LPR even when administered twice. Single administration of prednisolone significantly suppressed both the IPR and LPR.
  
  
  CONCLUSIONS
  These results indicate that PAF may be involved in the induction of biphasic cutaneous reactions mediated by IgE, and Y-24180 is more effective compared with WEB2086 in this model. It is possible that the difference in the effectiveness between Y-24180 and WEB2086 depends on the persistence of those activities.
authors.affiliation: Pharmaceutical Research, Yoshitomi Pharmaceutical Industries Ltd., Fukuoka, Japan. yamaguchi_shuji@yoshitomi.co.jp
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: N
authors.initials: N
authors.lastname: Tomomatsu
authors.forename: M
authors.initials: M
authors.lastname: Kagoshima
authors.forename: T
authors.initials: T
authors.lastname: Okumoto
authors.forename: H
authors.initials: H
authors.lastname: Komatsu
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology / Q000627:therapeutic use*; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004139:Dinitrofluorobenzene; D004423:Ear / Q000473:pathology; D004804:Eosinophils / Q000473:pathology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology*; D007700:Kinetics; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000473:pathology; D010972:Platelet Activating Factor / Q000502:physiology; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011239:Prednisolone / Q000494:pharmacology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine; D007073:Immunoglobulin E; D011239:Prednisolone; D004139:Dinitrofluorobenzene