(1)Bronchoconstrictors including histamine, methacholine, leukotriene D4, thromboxane A2 and neurokinin A fail to reliably evoke coughing in humans or in animals despite initiating reflex bronchospasm and mucus secretion, an increase in respiratory rate and dyspnea. This information can then be used to identify possible mechanisms for coughing in disease but may also suggest therapeutic approaches to restore normal cough function and sensitivity ( Table 1).
Knowing the specific ion channels and receptors for the stimuli that initiate cough is important, as this information can be used to identify which afferent nerves express these ion channels and receptors. cigarette smoke, toluene diisocyanate) activate the ion channel TRPA1. Cinnamaldehyde, AITC, and several other known respiratory irritants (e.g.
Bradykinin and PGE2 may also act in part through TRPV1 activation. For example, acids/ protons, capsaicin, resiniferetoxin and anandamide all act in part or entirely by activation of the ion channel/ receptor TRPV1. Although seemingly varied in origin and chemical composition, many of these stimuli share common modes of action. Other stimuli known to initiate coughing in animals and in human subjects include particulate/ dust, mechanical/ vibratory stimulation of the airway mucosa larynx or chest wall, chemical irritants such as resiniferetoxin, cinnamaldehyde and allylisothiocyanate (AITC), and the autacoids bradykinin, anandamide and prostaglandin E2 (PGE2). Several of these stimuli, including capsaicin, citric acid, hypertonic saline and low chloride buffers/ solutions, are often used to evoke cough experimentally. Multiple chemical and mechanical stimuli have been shown to initiate coughing in human subjects and in animals. Chemical and Mechanical Stimuli That Initiate Coughing
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