Participation of chemical mediators other than histamine in nasal allergy signs: A study using mice lacking histamine H₁ receptors

The purpose of this study was to investigate the involvement of chemical mediators other than histamine in nasal allergic signs using histamine H₁ receptor-deficient mice. In passively sensitized mice, antigen instillation into the nasal cavity induced significant increases in sneezing and nasal rubbing in wild-type mice, but no such increases were observed in histamine H₁ receptor-deficient mice. In actively sensitized mice, both sneezing and nasal rubbing were also significantly increased in a dose-dependent manner in both wild-type and histamine H₁ receptor-deficient mice. Histamine H₁ receptor antagonists such as cetirizine and epinastine significantly inhibited antigen-induced nasal allergic signs in wild-type mice, although the effects were incomplete. In addition, the thromboxane A₂ receptor antagonist ramatroban also inhibited these responses in wild-type mice. However, the leukotriene receptor antagonist zafirlukast showed no effects in wild-type mice. These results suggested that in the acute allergic model (passive sensitization), only histamine H₁ receptors are related to nasal signs induced by antigen, whereas in the chronic allergic model (active sensitization), both histamine H₁ receptors and thromboxane A₂ receptors were involved in the responses.