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.
D000403:Airway Resistance / Q000187:drug effects*; D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D004285:Dogs; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008761:Methylhistamines / Q000494:pharmacology; D008785:Metiamide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D011738:Pyrilamine / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000187:drug effects; D014132:Trachea / Q000187:drug effects
D008761:Methylhistamines; D011970:Receptors, Histamine H2; D008785:Metiamide; D006632:Histamine; D010047:Ovalbumin; D011738:Pyrilamine