Epithelial Irritant Receptors in the Lungs

J, Mills; Sellick, Hilary; Widdicombe, J. G.

doi:10.1002/9780470715352.ch7

Cited by 61 publications

(31 citation statements)

References 28 publications

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“…Koller (1967a, b; has shown that vagal afferent fibres in the guinea-pig are stimulated during pulmonary anaphylaxis; although he refers to them as " deflation receptors ", they are stimulated by inflation of the lungs and their properties indicate that they are probably identical to the "lung irritant receptors" studied in the rabbit (Homberger, 1968;Mills et al, 1969). These endorgans have terminals extending between the epithelial cells of the bronchial mucosa, are stimulated by intra-luminal chemical and mechanical irritants and by traction exerted on the bronchial wall, and cause reflex hyperpnoea and bronchoconstriction, and possibly also dyspnoea in man (Mills et al, 1969(Mills et al, , 1970.…”

Section: --H--h -H-h -mentioning

confidence: 77%

“…In the rabbit, both histamine, by intravenous injection or by inhaled aerosol, and anaphylaxis stimulate " lung irritant receptors " in the bronchial epithelium which are thought to cause vagal reflex hyperpnoea and bronchoconstriction (Mills et al, 1969(Mills et al, , 1970. It is reasonable to suppose that such receptors exist in other mammalian species, including the guinea-pig, and that they mediate the results described in this paper.…”

Section: --H--h -H-h -mentioning

confidence: 78%

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Role of the vagus nerves in anaphylaxis and histamine‐induced bronchoconstrictions in guinea‐pigs

J¹,

Widdicombe²

1970

British J Pharmacology

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135

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Summary1. The effects of vagotomy on the respiratory responses of guinea-pigs to anaphylactic reactions and to intravenous injections of histamine acid phosphate are described. 2. In spontaneously breathing guinea-pigs, vagotomy reduced by 50% or more the decreases in total lung conductance (bronchoconstriction) and the decreases in lung compliance, and almost abolished the rapid shallow breathing due to histamine.3. In paralysed, artificially ventilated guinea-pigs, vagotomy reduced by more than 33% the decreases in total lung conductance, but had little effect on the changes in lung compliance due to histamine. 4. In paralysed, artificially ventilated guinea-pigs, vagotomy reduced by 75% the decrease in total lung conductance and halved the decrease in lung compliance due to anaphylaxis. 5. We conclude that a vagal reflex is mainly responsible for the rapid shallow breathing due to histamine, and partly responsible for the bronchoconstrictions due to histamine and to anaphylaxis in guinea-pigs. We suggest that "lung irritant receptors" in the bronchial epithelium are the afferent end-organs involved.

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Section: --H--h -H-h -mentioning

confidence: 77%

Section: --H--h -H-h -mentioning

confidence: 78%

Role of the vagus nerves in anaphylaxis and histamine‐induced bronchoconstrictions in guinea‐pigs

J¹,

Widdicombe²

1970

British J Pharmacology

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135

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“…It is exceedingly unlikely that irritant receptors (Mills, Sellick & Widdicombe, 1970) are involved in the afferent pathway because (1) the slow manner in which the changes in lung volume were achieved is unlikely to have excited them, (2) their rapid adaptation does not fit with the long time constant of the response, (3) their increased rate of discharge produced by both inflation and deflation does not fit with the fact that the respiratory frequency response to inflation in our experiments was opposite to the response to deflation.…”

Section: Hi8tological 8tudie8 Of the Lung8mentioning

confidence: 99%

Studies of the pulmonary vagal control of central respiratory rhythm in the absence of breathing movements

Bartoli¹,

Bystrzycka²,

Guz³

et al. 1973

The Journal of Physiology

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SUMMARY1. Breuer's hypothesis that the vagus nerves exert a tonic control of respiratory rhythm, in addition to the phasic control, was examined.2. Closed-chest cardiopulmonary bypass was instituted in dogs weighing 20-30 kg anaesthetized with chloralose. Respiratory rhythm was recorded from a phrenic electroneurogram.3. Complete muscular paralysis induced with gallamine triethiodide produced an increase in the duration of inspiration and an increase in the amplitude of the integrated phrenic electroneurogram. There was no consistent effect on expiratory duration. Gallamine produced no effect when given after vagotomy.4. In the paralysed state, an increase in lung volume of 25-100 ml. for 30-60 sec produced a sustained increase in the duration of expiration and a decrease of respiratory rate: there was little effect on inspiratory duration, or the amplitude of the integrated phrenic electroneurogram.5. A decrease in lung volume of the same order of magnitude for the same period produced a sustained decrease in the duration of expiration and an increase of respiratory rate: there was little effect on inspiratory duration or the amplitude of the integrated phrenic electroneurogram. 6. The phenomena described in (5) and (6) constitute a high gain respiratory frequency controller. They did not occur after bilateral cervical vagotomy.7. Bilateral cervical vagotomy during complete muscular paralysis produced a further increase in the duration of inspiration and in the amplitude of the integrated phrenic electroneurogram; there was no consistent effect on expiratory duration.A. BARTOLI AND OTHERS 8. The results confirmed Breuer's hypothesis and showed that inspiratory duration and expiratory duration are controlled independently.

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“…RARs of the tracheobronchial tree and larynx showed similar responses to mechanical and some of the chemical irritants and are, therefore, identified under the common denomination of "irritant" receptors [16]. However, within this category of endings we find a wide range of distinctive characteristics, be this in terms of their responsiveness to aqueous solutions of varying osmolarity and composition [25,26] or to particular responses to substances produced within the body (autacoids) or administered experimentally [21,27,28].…”

Section: Discussionmentioning

confidence: 90%

“…The rate of adaptation varies considerably among RARs, with the most rapidly adapting endings responding only during changes in stretch with a behaviour similar to Pacinian corpuscles, showing a clear off-response at the removal of the stim-ulus [14]. RARs are very responsive to intraluminal stim-uli, mechanical probing of the mucosa, inhalation of inert dust, inflammatory mediators and oedema of the airway walls [15]; for this reason they have also been called irritant receptors [16]. The mechanosensitivity (response to inflation) of RARs is second only to that of slowly adapting receptors and higher than that of pulmonary and bronchial C-fibre endings [17].…”

mentioning

confidence: 99%

Action of moguisteine on the activity of tracheobronchial rapidly adapting receptors in the dog

Sant’Ambrogio¹,

Sant'Ambrogio²

1998

Eur Respir J

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Moguisteine is an antitussive agent with a novel chemical structure [1]. Its pharmacological activity has been tested on experimental animals and in several clinical trials. In guinea-pigs, moguisteine was found to reduce cough elicited by citric acid inhalation and electrical stimulation of the airway mucosa as effectively as codeine and dextromethorphan [2]. Moguisteine, injected into the cerebral ventricles of guinea-pigs, does not inhibit electrically stimulated cough, which is, instead, effectively blocked by intraventricular codeine: these findings suggest that the antitussive action of moguisteine depends on a peripheral mechanism [3]. Naloxone, a known narcotic antagonist, reverses the antitussive effects of codeine, but not those of moguisteine, indicating that the effects of moguisteine do not involve any interaction with opiate receptors. The antitussive action of moguisteine is also accompanied by clear anti-inflammatory effects in conditions characterized by bronchial hyperreactivity, airway leucocyte recruitment and airway microvascular leakage [4,5]. These anti-inflammatory effects of moguisteine have been found to be as strong as those of dexamethasone [4,5]. Several clinical trials have substantiated the beneficial effects of moguisteine on coughs of various nature: upper airway infection, chronic bronchitis, pulmonary fibrosis and tumours [6][7][8][9][10][11].Since cough is a reflex response elicited through the activation of specialized receptors activated by exogenous irritants and/or spontaneously occurring pathological conditions, the antitussive action of moguisteine could be viewed as dependent on an inhibitory effect on rapidly adapting irritant receptors (RARs). Indeed, the aim of this study was to investigate the possible effect of moguisteine on the activity of tracheobronchial RARs.RARs, as first identified by KELLER and LOESER [12] and later characterized with single fibre recordings by KNOWLTON and LARRABEE [13], represent a group of airway stretch receptors that respond to maintained lung in-flation and deflation with a rapidly adapting discharge at a highly irregular pattern of discharge. The rate of adaptation varies considerably among RARs, with the most rapidly adapting endings responding only during changes in stretch with a behaviour similar to Pacinian corpuscles, showing a clear off-response at the removal of the stim-ulus [14]. RARs are very responsive to intraluminal stim-uli, mechanical probing of the mucosa, inhalation of inert dust, inflammatory mediators and oedema of the airway walls [15]; for this reason they have also been called irritant receptors [16]. The mechanosensitivity (response to inflation) of RARs is second only to that of slowly adapting receptors and higher than that of pulmonary and bronchial C-fibre endings [17].RARs of similar nature are located superficially within the mucosa of both larynx and tracheobronchial tree [18]. RARs located in the large extrapulmonary tracheobronchial airways (trachea, main stem bronchi and proximal When the results a...

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Epithelial Irritant Receptors in the Lungs

Cited by 61 publications

References 28 publications

Role of the vagus nerves in anaphylaxis and histamine‐induced bronchoconstrictions in guinea‐pigs

Role of the vagus nerves in anaphylaxis and histamine‐induced bronchoconstrictions in guinea‐pigs

Studies of the pulmonary vagal control of central respiratory rhythm in the absence of breathing movements

Action of moguisteine on the activity of tracheobronchial rapidly adapting receptors in the dog

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