Histamine pharmacology in airway smooth muscle from a canine model of asthma

Tracheal smooth muscle (TSM) from an ovalbumin sensitized canine model of allergic asthma showed hypersensitivity and hyper-reactivity to histamine (H) when compared to that from littermate controls in vitro. Mepyramine abolished H responses in TSM of both groups; it also abolished the allergic response to obalbumin of TSM from sensitized dogs. The H2 receptor agonist, 4-methyl histamine (4-MH) caused small dose-related decreases in H contractures but had no effect on carbachol- or K+-induced tension. Metiamide, an H2 antagonist, did not enhance the H contracture, suggesting the 4-MH may not be exerting a relaxant effect since H2 receptors were absent. The maximum H-induced isometric tension was potentiated when the sensitized and control muscle strips were pre-equilibrated with 4-MH. These observations are consistent with the presence in canine TSM of H1 but not relaxant H2 receptors, the release of endogenous H to the tissue during the antigen-antibody reaction, and the competition of H and 4-MH for the H1 receptors. Experiments with specific blockers also indicated that in this model the only transmitter found in the ovalbumin-induced allergic bronchospasm was histamine.