An analysis of the functional interactions of selected contractile agonists in the Guinea pig isolated trachea

Functional interactions between several contractile agonists were examined in the guinea pig isolated trachea. Cumulative concentration-response effects of agonist A were obtained in the absence and presence of steady-state contractions induced by agonist B. The agonists examined included histamine, prostaglandin D₂, platelet activating factor, leukotrienes E₄ and D₄ and carbamylcholine. We found that none of the agonists studied caused a leftward shift in the concentration-response curve of a second agonist, nor did nay agonist decrease the concentration of a second agonist required to evoke a maximum response. In general the functional interactions fit the predictions based on the early models of functional additivity. However, the interactions deviated categorically from this model in that there was less than predicted additivity at concentrations of the interactants that alone induced greater than a 50% response. The degree to which this deviation occurred was agonist dependent. The results that in the guinea pig trachea a contractile agonist does not uncover or increase a reserve in the receptor-subeffect-response chain of a second contractile agonist. The finidngs that the quantitative nature of the interactionss were somewhat agonist dependent supports the hypothesis that more than one biochemical mechanism is involved in the receptor-mediated contraction of airway smooth muscle.