Suppressive effects of Y-24180, a receptor antagonist to platelet activating factor (PAF), on antigen-induced asthmatic responses in guinea pigs.
OBJECTIVE
Effects of Y-24180 on antigen-induced asthmatic responses were evaluated in actively sensitized guinea pigs and the effects were compared with those of several anti-asthmatic drugs.


METHODS
Male Hartley guinea pigs were used.


METHODS
Guinea pigs were actively sensitized with ovalbumin and were pretreated with pyrilamine Y-24180 was orally administered to the animals 3 h and others were 1 h before the antigen challenge.


METHODS
The airway hyperresponsiveness was measured according to the method of Konzett and Rössler with some modifications. The immediate asthmatic response (IAR) and late asthmatic response (LAR) were measured by the oscillation method. Inflammatory cells infiltrated into the lungs were counted after the bronchoalveolar lavage.


RESULTS
Under oral administration before or after the challenge with antigen, Y-24180, OKY-046, and ONO-1078 suppressed the antigen-induced airway hyperresponsiveness. Moreover, Y-24180, ONO-1078, AA-2414, and theophylline suppressed both the IAR and LAR, but OKY-046 only suppressed the LAR. Among the test drugs, only Y-24180 and theophylline suppressed the antigen-induced accumulation of eosinophils in the bronchoalveolar lavage fluid.


CONCLUSIONS
The data indicate practical participation of PAF in the development of antigen-induced asthmatic responses in animals, and usefulness of Y-24180 in the clinical treatment of asthma as well as other anti-asthmatic drugs.
Kagoshima
M
M
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Tomomatsu
N
N
Iwahisa
Y
Y
Yamaguchi
S
S
Matsuura
M
M
Kawakami
Y
Y
Terasawa
M
M
D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016227:Benzoquinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020024:Leukotriene Antagonists; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010047:Ovalbumin / Q000008:administration & dosage / Q000633:toxicity; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011738:Pyrilamine / Q000008:administration & dosage / Q000494:pharmacology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000336:Aerosols; D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D001381:Azepines; D016227:Benzoquinones; D001993:Bronchodilator Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D006633:Histamine Antagonists; D020024:Leukotriene Antagonists; D008689:Methacrylates; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015842:Serine Proteinase Inhibitors; D014230:Triazoles; C039351:platelet activating factor receptor; 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; C060230:seratrodast; D010047:Ovalbumin; D013806:Theophylline; D013930:Thromboxane-A Synthase; D011738:Pyrilamine; C034364:ozagrel; C047681:pranlukast