To seek evidence for the involvement of acetylcholinesterase activity in the modulatory influence of the airway epithelium, we examined responses to acctylcholine (ACh), hcthancchol, histamine or KCI in isolated epithelium-intact and epithelium-denuded guinea-pig trachcalis preparations. The concentration-response curves to ACh were shifted 26-fold to the left by epithelial denudation hut the contractile response to KCl was not altered. The response to histamine in epithelium-denuded preparations increased 4-fold with no attenuation in the presence of physostigmine (30 nM). Physostigmine (30 nM) potentiated the response to ACh in epithelium-intact tissues more (about 26-fold) than in epithelium-denuded tissues (about 3.5-fold). Thus, in the presence of physostigmine removing the epithelium had only a slight effect (not statistically significant) on the potency of ACh to contract the trachea. Removing the epithelium had no effect on the potency of bethanechol, a muscarinic receptor agonist that is not a substrate for cholincsicrases. Physostigmine itself contracted the trachealis muscle but the pD2 values and maximum responses in epithelium-intact and denuded preparations were not significantly different. The frequency-response curves to electrical field-stimulated cholinergic contractions were unaffected by removing the epithelium. In conclusion, the principal mechanism by which the epithelium inhibis contraction of guinea-pig trachea to exogenously applied ACh is via epithelium-derived acetylcholinesterase activity.
- (epithelium-derived relaxing factor)
- Electrical field stimulation
- Epithelium-derived acetylcholinesterase
- Trachealis muscle (guinea-pig)
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