Abstract
The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS) respond to electric field stimulation (EFS) and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM) caused bronchoconstriction in human (4 from 7) and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC). However, this effect was notably smaller in human responder (30±7.1%) than in guinea pig (79±5.1%) PCLS. The transient receptor potential (TRP) channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.
Highlights
Airway smooth muscle (ASM) contraction is mainly controlled by autonomic neurons innervating the airways and the lung
Since the mouse is such a common laboratory animal, we examined whether neural activation is possible at all in mouse precision-cut lung slices (PCLS) by using harsher electric field stimulation (EFS) conditions
In the present study an electric field was applied to PCLS from different mammals allowing the comparison of neuronally triggered airway responses under identical conditions
Summary
Airway smooth muscle (ASM) contraction is mainly controlled by autonomic neurons innervating the airways and the lung. The relative tissue content of the neuropeptides substance P and calcitonin gene related peptide (CGRP) is much higher in guinea pigs than in rabbits or marmosets [3]. Neurotransmission can be modulated differently, e.g. cholinergic neurotransmission is facilitated by neurokinin receptors in rabbit (NK1- and NK2receptor) and guinea pig (NK1 receptor) airways, whereas those receptors have no effect in human airways [5]. Lung innervation is heterogeneous and extrapolation of pharmacological interventions from laboratory animals to the human situation is difficult. Given all these problems it appears important to identify an experimental animal model that reflects the human situation
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