Irritant receptors

When the pulmonary response is activated by irritant receptors in the nose, response for different flows and concentrations would not be expected to correlate with the volume of inspired gas, but rather with regional dosage (e.g., nasal) or the local dosage of gas to irritant receptors lining the airway. ... 

It is believed that it acts by two mechanisms selective anesthesia of irritated receptors in the lungs and simultaneous suppression of the cough center. Synonyms of this drug are tes-salon, ventussin, and others. 

Kasanen, J.-P., Pasanen, A.-L., Hesvuori, J., Kosma, V.-M. and Alarie, Y. (1998) Stereospedfidty of the sensory irritation receptor for nonreactive chemicals illustrated by pinene enantiomers. Archives of Toxicology, 72 (8), 514—23. 

Another postulated mechanism is an altered function of the central nervous and respiratory systems through an amplification of a nonspecific inflammatory response to low-level irritants (neurogenic inflammation hypothesis). This suggests that MCS may be initiated by the interaction of chemical irritants with sensory nerves or C-fiber neurons, a nonspecific response pathway. It is proposed that inhaled chemicals stimulate irritation receptors which activate sensory nerves to release mediators producing vasodilation, edema, and other manifestations of inflammation, leading to neurogenic inflammation. There is some evidence in animals for this theory. 

Animal testing to determine irritant properties and thresholds has become standard. A consensus method, American Society for Testing and Materials E, is widely regarded as the basis. This method has been used to develop structure-activity relationships, to demonstrate that more than one irritant receptor may exist in the trigeminal nerve, and to explore the interaction of multiple exposures. Recently, it has been used to demonstrate the irritating properties of office equipment offgassing. 

Three different mechanisms have been proposed to explain the reaction to sulfites in asthmatic patients. The first is explained by the inhalation of sulfur dioxide, which produces bronchoconstriction in aU asthmatics through direct stimulation of afferent parasympathetic irritant receptors. Furthermore, inhalation of atropine or the ingestion of doxepin protects sulfite-sensitive patients from reacting to the ingestion of sulfites. The second theory, IgE-mediated reaction, is supported by reported cases of sulfite-sensitive anaphylaxis reaction in patients with positive sulfite skin test. Finally, a reduced concentration of sulfite oxidase enzyme (the enzyme that catalyzes oxidation of sulfites to sulfates) compared with normal individuals has been demonstrated in a group of sulfite-sensitive asthmatics. 

Ashton et al. (1977) exposed human volunteers to a 1-2 pm aerosol of concentration 0.25 mg m-3 for 1 h. Peak expiratory flow was decreased by 7% after 20 min of exposure, which the investigators considered was due to pulmonary irritant receptors causing bronchoconstriction. 

Exercise-Induced Asthma. In some asthmatics (usually young, allergic patients) moderate to severe exercise can initiate an asthmatic attack. As with intrinsic asthma, the etiology of exercise-induced asthma has not been well defined. One theory (Deal et al, 1979) suggests that cold-sensitive irritant receptors in the epithelia are associated with afierent nerve fibers within an autonomic reflex arc. Efferent motor fibers of this reflex then return to the airway smooth muscle via the vagus nerve. Thus, bronchoconstriction is induced through this reflex arc by stimulation of the cold-sensitive irritant receptors. 

Environmental or Occupational Asthma. With modern industrialization, the concentration of airborne pollutants in the environment has increased and led to the development of an environmental form of asthma, which can occur in individuals living in concentrated industrial areas. This type of asthma appears to result from exposure of individuals to toxic gases such as sulfur dioxide. Because of their hyperirritable airways, all types of asthmatics are effected by such environmental pollution, but there is one class that has no other underlying etiology besides an increased sensitivity to polluted air. In these individuals, exposure to environmental pollution is hypothesized to stimulate irritant receptors in the lung. 

Not all cases of asthma can be attributed to reaction to an allergen. Other stimuli that cause asthma attacks include exercise, cold air, infections and atmospheric pollutants. In these cases symptoms may be produced through stimulation of irritant receptors and release of mediators from sensory neurones. Treatment of asthma of whatever cause is by use of bronchodilators to reverse the bronchospasm of the immediate phase and by anti-inflammatory dmgs to inhibit or prevent the development of the late phase. 

P2 adrenoreceptor stimulants are used as first choice for the rapid relief of an acute asthmatic attack and maintenance treatment of chronic asthma. They are more effective in treatment of the immediate phase reaction than the late phase reaction. P2 adrenoreceptor stimulants are less effective in chronic bronchitis, possibly because in this disease bronchoconstriction is due to reflex stimulation of acetylcholine receptors following stimulation of local irritant receptors in lung tissue. 

Romanelli MN, Gualtieri F (2003) Cholinergic nicotinic receptors Competitive ligands, allosteric modulators, and their potential applications, Med Res Rev 23 393-426 Sampson SR, Vidruk EH (1975) Properties of irritant receptors in canine lung, Respir Physiol 25 9-22... 

Sellick H, Widdicombe JG (1971) Stimulation of lung irritant receptors by cigarette smoke, carbon dust, and histamine aerosol, J Appl Physiol 31 15-19 Simpson PB, Challiss RA, Nahorski SR (1995) Neuronal Ca + stores Activation and function. Trends Neurosci 18 299-306... 

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