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  • Title: Acetylcholine and histamine interact supra-additively on bronchomotor tone in guinea-pigs in vivo: a possible consequence of the relationship between airways resistance and calibre.
    Author: Stewart AG, Thompson DC, Fennessy MR.
    Journal: Arch Int Pharmacodyn Ther; 1985 Jan; 273(1):33-46. PubMed ID: 4004415.
    Abstract:
    Histamine and acetylcholine administered simultaneously to anaesthetized guinea-pigs result in a bronchoconstriction greater than that of the sum of the individual bronchoconstrictor effects of histamine and acetylcholine administered separately, i.e., a supra-additive interaction. In contrast, a supra-additive effect of acetylcholine and histamine on the isolated tracheal strip did not occur. At a pretreatment concentration of acetylcholine of 5 microM, histamine concentration-response curves were shifted rightwards, i.e., a less than additive interaction, suggesting that, at higher concentrations, histamine and acetylcholine do not act as independent agonists on guinea-pig tracheal smooth muscle. There was no supra-additive interaction between histamine and acetylcholine on tracheal segment tension when measured in situ. These observations suggest that there is no direct interaction between histamine and acetylcholine on the airways smooth muscle cell capable of explaining the supra-additive interaction in vivo. Hexamethonium pretreatment did not alter the magnitude of this supra-additive interaction indicating that an indirect interaction involving autonomic control of airways calibre does not contribute to this phenomenon. The selectivity of the supra-additive interaction for changes in airways resistance rather than compliance, together with the negative evidence for either a direct or an indirect pharmacological interaction between histamine and acetylcholine, suggest that the interaction may result from the physical relationship between airways resistance and airways calibre.
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