Transduction mechanisms in airway sensory nerves (original) (raw)
Related papers
Airway receptors and their reflex function--invited article
Advances in experimental medicine and biology, 2009
Sensory information in the lung is generated by airway receptors located throughout the respiratory tract. This information is mainly carried by the vagus nerves and yields multiple reflex responses in disease states (cough, bronchoconstriction and mucus secretion). Airway receptors are also essential for breathing control and lung defense. A single sensory unit contains homogeneous or heterogeneous types of receptors, providing varied and mixed behavior. Thus, the sensory units are not only transducers, but also processors that integrate information in different modes.
Effects and interactions of sensory neuropeptides on airway microvascular leakage in guinea-pigs
British Journal of Pharmacology, 1988
1 We have studied the effect of the sensory neuropeptides substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) on microvascular permeability in guinea-pig airways in vivo and investigated whether CGRP would potentiate the effect of SP. We used the extravasation of intravenously-injected Evans blue dye as an index of permeability. 2 The tachykinins SP, NKA and NKB (0.025-5.Onmol kg-, i.v.) significantly (P <0.05) increased extravasation of dye in a dose-related manner and with a similar pattern of distribution; they were most potent in the trachea and main bronchi, less potent in the larynx and intrapulmonary airways, and had little significant effect in the bladder.
Effect of Extracellular Calcium on Excitability of Guinea Pig Airway Vagal Afferent Nerves
Journal of Neurophysiology, 2002
The effect of reducing extracellular calcium concentration ([Ca2+]o) on vagal afferent excitability was analyzed in a guinea pig isolated vagally innervated trachea-bronchus preparation. Afferent fibers were characterized as either having low-threshold, rapidly adapting mechanosensors (Aδ fibers) or nociceptive-like phenotypes (Aδ and C fibers). The nociceptors were derived from neurons within the jugular ganglia, whereas the low-threshold mechanosensors were derived from neurons within the nodose ganglia. Reducing [Ca2+]o did not affect the excitability of the low-threshold mechanosensors in the airway. By contrast, reducing [Ca2+]o selectively increased the excitability of airway nociceptors as manifested by a substantive increase in action potential discharge in response to mechanical stimulation, and in a subset of fibers, by overtly evoking action potential discharge. This increase in the excitability of nociceptors was not mimicked by a combination of ω-conotoxin and nifedipin...
Life Sciences, 2007
The role of extracellular acidosis in inflammatory airway diseases is not well known. One consequence of tissue acidification is the stimulation of sensory nerves via the polymodal H + -gated transmembrane channels ASICs and TRPV1 receptor. The present study investigated the effect of acidosis on airway basal tone and responsiveness in the guinea pig. Acidosis (pH 6.8, 10 min, 37°C) significantly decreased the basal tone of tracheal rings (p b 0.01 vs. paired control). Moreover, pH fall raised the maximal contraction of tracheal rings to acetylcholine (p b 0.05 vs. paired control). The pH-induced relaxation of airway basal tone was inhibited by pretreatments with ASIC1a or ASIC3/ASIC2a inhibitors (0.5 mM ibuprofen, 0.1 mM gadolinium), nitric oxide synthase inhibitor (1 mM L-NAME), and guanylate cyclase inhibitor (1 μM ODQ). In contrast, the pH-induced relaxation of airway basal tone was not modified by epithelium removal or pretreatments with a TRPV1 antagonist (1 μM capsazepine), a combination of NK 1,2,3 receptor antagonists (0.1 μM each), a blocker of voltage-sensitive Na + channels (1 μM tetrodotoxin), a cyclooxygenase inhibitor with no activity on ASICs (1 μM indomethacin) or ASIC3 and ASIC3/ASIC2b inhibitors (10 nM diclofenac, 1 μM aspirin). Furthermore, acid-induced hyperresponsiveness to acetylcholine was inhibited by epithelium removal, capsazepine, NK 1,2,3 receptor antagonists, tetrodotoxin, amiloride, ibuprofen and diclofenac. In summary, the initial pH-induced airway relaxation seems to be independent of sensory nerves, suggesting a regulation of airway basal tone mediated by smooth muscle ASICs. Conversely, the pH-induced hyperresponsiveness involves sensory nerves-dependent ASICs and TRPV1, and an unknown epithelial component in response to acidosis.
Reflex regulation of airway sympathetic nerves in guinea-pigs
The Journal of Physiology, 2006
Sympathetic nerves innervate the airways of most species but their reflex regulation has been essentially unstudied. Here we demonstrate sympathetic nerve-mediated reflex relaxation of airway smooth muscle measured in situ in the guinea-pig trachea. Retrograde tracing, immunohistochemistry and electrophysiological analysis identified a population of substance Pcontaining capsaicin-sensitive spinal afferent neurones in the upper thoracic (T1-T4) dorsal root ganglia (DRG) that innervate the airways and lung. After bilateral vagotomy, atropine pretreatment and precontraction of the trachealis with histamine, nebulized capsaicin (10-60 μM) evoked a 63 ± 7% reversal of the histamine-induced contraction of the trachealis. Either the β-adrenoceptor antagonist propranolol (2 μM, administered directly to the trachea) or bilateral sympathetic nerve denervation of the trachea essentially abolished these reflexes (10 ± 9% and 6 ± 4% relaxations, respectively), suggesting that they were mediated primarily, if not exclusively, by sympathetic adrenergic nerve activation. Cutting the upper thoracic dorsal roots carrying the central processes of airway spinal afferents also markedly blocked the relaxations (9 ± 5% relaxation). Comparable inhibitory effects were observed following intravenous pretreatment with neurokinin receptor antagonists (3 ± 7% relaxations). These reflexes were not accompanied by consistent changes in heart rate or blood pressure. By contrast, stimulating the rostral cut ends of the cervical vagus nerves also evoked a sympathetic adrenergic nerve-mediated relaxation that were accompanied by marked alterations in blood pressure. The results indicate that the capsaicin-induced reflex-mediated relaxation of airway smooth muscle following vagotomy is mediated by sequential activation of tachykinin-containing spinal afferent and sympathetic efferent nerves innervating airways. This sympathetic nerve-mediated response may serve to oppose airway contraction induced by parasympathetic nerve activation in the airways.
British Journal of Pharmacology, 1990
In the present study we have examined whether neuropeptide Y (NPY) interferes with non-adrenergic, non-cholinergic nerve-mediated contractions and relaxations in the guinea-pig airways. In these experiments we have used ring preparations of bronchi and trachea, incubated in the presence of atropine, propranolol and indomethacin (each 1 yM). 2 The contractile response to electrical stimulation of non-adrenergic, non-cholinergic nerve fibres was suppressed by NPY and NPY 13-36 in a concentration-dependent manner, these agents having similar inhibitory potencies. NPY caused a more complete inhibition than the C-terminal fragment. 3 NPY affected neither the basal tension nor the substance P-evoked contraction in the bronchi and trachea and did not interfere with nerve-mediated, non-adrenergic relaxation in the trachea. 4 On the basis of these results, it is suggested that NPY may act on the terminals of sensory neurones in the airways to prevent antidromic, excitatory neurotransmission by inhibiting transmitter release.
British Journal of Pharmacology, 2001
1 Nerve growth factor induces an airway hyperresponsiveness in vivo in guinea-pigs, as we have shown previously. Since antagonizing the neurokinin-1 (NK 1 ) receptor can prevent this NGFinduced airway hyperresponsiveness and since sensory nerves release tachykinins, we investigated the role of sensory nerves in the NGF-induced airway hyperresponsiveness. 2 We used isolated tracheal rings from guinea-pigs to measure tracheal contractility. In these rings sensory nerve endings are present, but these endings lack any contact with their cell bodies.