The role of histamine receptors in asthma.
1. Eighteen non-asthmatic and 18 asthmatic subjects underwent challenge with increasing doses of histamine from a dosimeter-nebulizer system. Half the subjects in each group were atopic and half non-atopic. Bronchial response was monitored with serial measurements of specific airways conductance (sGaw) and a dose-response curve was constructed for each challenge. In addition, the nine atopic asthmatic patients underwent antigen challenges with a similar technique. In each subject the challenges were repeated, on separate days, after intravenous injections of either sodium chloride solution (150 nmol/l: saline) placebo, chlorpheniramine (an H1-receptor antagonist), cimetidine (an H2-receptor antagonist) or after both antagonists together. Baseline bronchial tone was always comparable within subjects immediately before challenge. 2. Cimetidine had no significant effect on baseline sGaw in any group, whereas chlorpheniramine raised baseline sGaw in the asthmatic subjects. Placebo did not alter the mean dose-response curves for histamine or antigen. However there was a small, but significant, shift of the curves to the right after cimetidine and a much larger shift to the right with chlorpheniramine, whether given alone or with cimetidine. The effect of the histamine antagonists on histamine and antigen responses was very similar and there was no difference in the pattern of response among normal subjects as compared with asthmatics or among atopic as compared with non-atopic subjects. 3. In conclusion, the same pattern of histamine receptors exists in the airways of asthmatic and normal subjects. Histamine-induced bronchoconstriction is mediated predominantly via the H1-receptors, with little, if any, contribution from the H2-receptors. Histamine appears to be an important mediator in the immediate allergic response in airways since this response is blocked by an H1-receptors antagonist.
D000403:Airway Resistance / Q000187:drug effects; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000503:physiopathology; D011968:Receptors, Histamine / Q000502:physiology*
D011968:Receptors, Histamine; D002744:Chlorpheniramine; D002927:Cimetidine