Allergen-induced biphasic bronchoconstriction in rats.
The development of an allergic bronchoconstriction model in rats is described. In actively sensitized Donryu strain rats, there was a remarkable biphasic increase in airway resistance within 10 min after antigen challenge on day 9 to day 21. The increase in airway resistance, correlated with the IgE titer and the dose of antigen, was inhibited by disodium cromoglycate (DSCG) or by aminophylline. This bronchoconstriction was remarkably blocked by methysergide (25 and 100 micrograms/kg) while pyrilamine inhibited it partially at the same dose. Serotonin (greater than 30 micrograms/kg) but not histamine (less than 1,000 micrograms/kg) induced a bronchoconstriction. FPL-55712 (1,10 mg/kg) inhibited it significantly. The content of thromboxane B2 (TxB2) in plasma increased during the bronchoconstriction while the content of peptide-leukotrienes (p-LTs) in plasma did not increase significantly. OKY-046 inhibited not only allergic bronchoconstriction but also the increase in TxB2 levels in plasma. The late phase of the bronchoconstriction was more susceptible to OKY-046. In conclusion, this model seems to be useful for the screening of antiasthma drugs because of a relationship with the dose of antigen, IgE titer and the susceptibility to an antiallergic drug or a bronchodilator. It is demonstrated that the major part of this allergic bronchoconstriction depends on serotonin, and it is also suggested that thromboxane A2 may play an important role in the late phase of the bronchoconstriction.
Watanabe
A
A
Department of Pharmacology, Toyobo Co., Ohtsu, Japan.
Hayashi
H
H
D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000276:immunology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001986:Bronchial Spasm / Q000276:immunology*; D002867:Chromones / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D006632:Histamine / Q000494:pharmacology; D006967:Hypersensitivity / Q000276:immunology*; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains / Q000276:immunology*; D012701:Serotonin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors
D000485:Allergens; D002867:Chromones; D015289:Leukotrienes; D008689:Methacrylates; D000628:Aminophylline; D012701:Serotonin; D013929:Thromboxane B2; D006632:Histamine; C006312:FPL 55712; D011738:Pyrilamine; C034364:ozagrel; D004205:Cromolyn Sodium; D008784:Methysergide