The reactivity of the trachealis smooth muscle of the isolated, perfused male English-guinea-pig trachea to methacholine (62511), histamine (51456) and isoproterenol (7683592) was compared after the drugs were applied to the intraluminal (IL) or extraluminal (EL) surfaces. All agents were more potent when added to the EL component but the IL/EL median effective concentration ratios were different being 100 for methacholine, 41 for histamine, and 25 for isoproterenol. Methacholine or histamine added to the IL compartment, after the preparations were precontracted with the same concentration of the agonist of 30 millimolar potassium-chloride (KCL) added EL, did not result in relaxation. Similarly IL isoproterenol did not evoke contraction. IL KCl evoked relaxation. The authors conclude that the epithelium reduces access of bronchoactive agents to the muscle while an immediate relaxant effect of epithelium derived relaxing factor released by agonists could not be demonstrated.
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