Characteristics of histamine H4 receptor agonist-induced allergic conjunctivitis model in Guinea pigs

Abstract

Histamine is strongly associated with the onset of allergic conjunctivitis. The most recent cloned histamine H₄ receptor antagonist is highly expected as a new therapeutic drug candidate. As a model for a therapeutic drug targeting the histamine H₄ receptor, a mouse model in which conjunctivitis symptoms are induced by instilling 4-methylhistamine, a histamine H₄ receptor agonist, has been reported. However, the affinity of the H₄ receptor for histamine varies in species, and it is known that the histamine binding affinity for the guinea pig H₄ receptor is closer to that for human receptor than mice receptor. In this paper, we investigated a possibility that a guinea pig model would become a drug efficacy evaluation model with higher evaluation accuracy than the mouse model.

As a result, hyperemia was observed in the conjunctivae and iris of guinea pigs after instillation of 4-methylhistamine and specifically suppressed by the histamine H₄ receptor antagonist. Unlikely to the previously reported mouse model, however, none of edema, increased vascular permeability or scratching behavior was observed, suggesting that there may be differences between mice and guinea pigs not only in the binding affinity of histamine to the H₄ receptor but also in the biological reaction to 4-methylhistamine. Although the symptoms of allergic conjunctivitis do not appear comprehensively in the guinea pig model, results of this study indicated a possibility that this model can be used as a simple screening model in the early stages of drug development.