Effect of Y-24180, a receptor antagonist to platelet-activating factor (PAF), on allergic cutaneous reactions in actively sensitized mice.

Abstract

OBJECTIVE AND DESIGN:

We examined the effect of Y-24180, a potent antagonist to platelet-activating factor (PAF), on allergic cutaneous reactions in actively sensitized mice.

MATERIALS:

Male BALB/c and BALB/c-nu/nu mice were used.

TREATMENT:

Y-24180, ketotifen fumarate (ketotifen), and suplatast tosilate (suplatast) were orally administered twice a day for 3 days beginning 2 days before an ovalbumin (OA) challenge. Hydrocortisone 17-butyrate (hydrocortisone) was applied topically to ear surface once a day for 3 days, beginning 2 days before the OA challenge.

METHODS:

Mice actively sensitized with OA were challenged by intradermally injecting OA into both ears. Ear thickness was measured with a dial thickness gauge.

RESULTS:

Increase in ear thickness, with peak responses at 1 h (immediate phase reaction, IPR) and 24 h (late phase reaction, LPR) after the challenge, were induced in actively sensitized BALB/c mice. The reactions were not induced in T cell-deficient BALB/c-nu/nu mice. Y-24180 suppressed both the IPR and LPR of BALB/c mice. Although suplatast suppressed the LPR, the IPR was not affected. Ketotifen suppressed the IPR, but not the LPR. Hydrocortisone suppressed both the IPR and LPR of BALB/c mice. Furthermore, Y-24180 in combination with hydrocortisone significantly enhanced the effect of hydrocortisone on both the reactions.

CONCLUSIONS:

Y-24180 was demonstrated not only to suppress the IPR and LPR, but also to show strong suppressive effects in combination with topical hydrocortisone. Therefore, Y-24180 is expected to contribute to the treatment of inflammatory skin diseases including atopic dermatitis.

• Authors: S Yamaguchi, N Tomomatsu, H Komatsu
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 49 Issue 11 Pg. 584-90 (Nov 2000) ISSN: 1023-3830 [Print] Switzerland
• PMID: 11131298 (Publication Type: Journal Article)

Chemical References

• Allergens
• Anti-Allergic Agents
• Anti-Inflammatory Agents
• Arylsulfonates
• Azepines
• Histamine H1 Antagonists
• Immunoglobulin G
• Platelet Membrane Glycoproteins
• Receptors, Cell Surface
• Receptors, G-Protein-Coupled
• Sulfonium Compounds
• Triazoles
• platelet activating factor receptor
• 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
• Immunoglobulin E
• Ovalbumin
• suplatast tosilate
• Hydrocortisone
• Ketotifen

Topics

• Administration, Oral
• Administration, Topical
• Allergens (immunology)
• Animals
• Anti-Allergic Agents (administration & dosage, pharmacology)
• Anti-Inflammatory Agents (pharmacology)
• Arylsulfonates (administration & dosage, pharmacology)
• Azepines (administration & dosage, pharmacology)
• Dermatitis, Allergic Contact (immunology, pathology)
• Ear (pathology)
• Eosinophils (immunology)
• Histamine H1 Antagonists (administration & dosage, pharmacology)
• Hydrocortisone
• Immunoglobulin E (blood)
• Immunoglobulin G (blood)
• Ketotifen (administration & dosage, pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Ovalbumin (immunology)
• Platelet Membrane Glycoproteins (antagonists & inhibitors)
• Receptors, Cell Surface
• Receptors, G-Protein-Coupled
• Sulfonium Compounds (administration & dosage, pharmacology)
• Time Factors
• Triazoles (administration & dosage, pharmacology)