Histamine H3 receptors modulate antigen-induced bronchoconstriction in guinea pigs

The effects of a histamine H3-receptor antagonist on the bronchoconstrictor response to antigen challenge were studied in sensitized guinea pigs. We monitored airway opening pressure as an index of airway caliber, and the provocative dose of intravenous ovalbumin (OA) required to produce 200% increase in airway opening pressure (PD200) was determined. Animals were pretreated with propranolol to inhibit adrenergic bronchodilation. OA (1 to 100 micrograms/kg intravenously) challenge caused significant bronchoconstriction with a PD200 of 28.8 micrograms/kg (geometric mean). The selective H3-antagonist, thioperamide (5 mg/kg intraperitoneally), significantly enhanced the OA-induced bronchoconstriction with the PD200 value decreased to 4.0 micrograms/kg (p less than 0.001). The H2-antagonist, cimetidine (10 mg/kg intraperitoneally), had no significant effect on OA-induced response (PD200, 18.2 micrograms/kg). The H1-antagonist, mepyramine (10 mg/kg intraperitoneally), almost completely blocked the effect of OA, suggesting that OA-induced bronchoconstrictor responses are histamine (H1 receptor) mediated. Thioperamide did not alter the dose-response curve to exogenous histamine (0.3 to 3 micrograms/kg intravenously). We conclude that H3 receptors might play a role in regulation of antigen-induced response in the airways.