1In order to examine the role of airway epithelium in the responsiveness of smooth muscle in man, we measured the contractile responses to acetylcholine (ACh), histamine, and prostaglandin F2, (PGF2,) and the relaxation response to isoprenaline (Isop), in 48 bronchi obtained from 10 patients who received surgery. Responses were measured in the presence and absence of the epithelium. 2 Removal of epithelium (by rubbing the mucosa gently with forceps) significantly increased the contractile responses evoked by ACh, histamine and PGF2,.3 In contrast, removal of epithelium did not alter the relaxation response to Isop. 4 To clarify the mechanism underlying this epithelial inhibitory effect on smooth muscle contraction, we measured the contractile responses of dog trachea with the epithelium removed to increasing concentrations of ACh. After measuring the control response, we added about 0.1 g of the chopped epithelium in the organ chamber, and measured the response again. 5 After adding airway epithelium and incubating with tracheal strips, the contractile response of tracheal strips decreased significantly as compared to the control response. 6 These results show that airway epithelium possesses the ability to decrease the smooth muscle contraction to ACh, histamine and PGF2X in man and dogs.7 The mechanism of this inhibitory effect of the airway epithelium is not explained by a change in mechanical property of the airway nor the change in diffusion of these drugs to the smooth muscle across the epithelium. Thus, these results suggest that airway epithelium may have an important role in modulating smooth muscle tone, possibly by inactivation of these mediators, or by releasing an epithelium-derived relaxing factor.

To elucidate the effect of endogenous tachykinins on neuro-effector transmission of vagal nerves, we performed in vitro experiments using guinea-pig tracheal smooth muscle. The subthreshold dose (the highest dose which did not induce any smooth muscle contraction) of capsaicin (10^-8 to 10^-7 M) increased the amplitudes of contractions evoked by electrical field stimulation (EFS) significantly, but not those by acetylcholine (ACh). The inhibitor of neutral endopeptidase, phosphoramidon (10^-7 to 10^-6M), increased the contractions evoked by EFS significantly. The inhibitor of cholinesterase, physostigmine (10^-6 to 10^-5M), induced smooth muscle contractions, but such contractions were inhibited by atropine, suggesting the spontaneous release of ACh from the vagal nerve terminals. The subthreshold dose of substance P or capsaicin increased the contractions evoked by physostigmine. These results indicated that endogenous tachykinins increase the spontaneous ACh release as well as the ACh release in response to vagal stimulation from the nerve terminals. Furthermore, it is suggested that the excitatory effects of the tachykinins on the vagal neuro-effector transmission may be modulated by neutral endopeptidase in the guinea pig

Background: The vagus nerve is reported to play an important role in the regulation of airway responsiveness. Objective: In the present study, we investigated the role of the local vagus nerve in the changes in isometric tension of smooth muscle induced by histamine in the human airway. Methods: Eight human lung tissue specimens were obtained at thoracic surgery, and 24 bronchial smooth muscle strips were used for isometric tension recording. The changes in isometric tension were induced by histamine in the presence or absence of physostigmine (10^–6 M), atropine (10^–6 M), and/or tetrodotoxin (10^–6 M). Results: We found that: (1) histamine induced a dose-dependent increase in the isometric tension in human bronchial smooth muscle; (2) physostigmine (10^–6 M) significantly potentiated the amplitude of the histamine-induced increase in isometric tension; (3) atropine (10^–6 M) significantly suppressed the histamine-induced increase in isometric tension; (4) tetrodotoxin (10^–6 M), did not affect the histamine-induced increase in isometric tension of smooth muscle, and (5) in the presence of tetrodotoxin, atropine significantly suppressed the histamine-induced increase in isometric tension. Conclusion: These findings suggest that the histamine-induced increase in isometric tension is mediated partly by acetylcholine, presumably released by the direct action of histamine on the vagus efferent nerve terminals without the central reflex via vagus nerve.

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