Laryngeal chemoreceptors (TRPV1; acid‐sensitive ion channels, ASIC; and osmotic receptors) and mechanoreceptors play an important role in triggering apnea, especially in infants, which has been related to the pathogenesis of sudden infant death syndrome (SIDS). LA, a main flavonoid component of licorice widely used as an antitussive herbal medicine in China even via taking lozenge, is reportedly able to suppress cough responses to inhalation of aerosolized capsaicin (a selective stimulant of TRPV1) in conscious guinea pigs. These results imply an inhibitory impact of LA on airway TRPV1; however, it remains unknown whether LA affects the apneic responses to selective stimulation of these laryngeal receptors, and if so whether its effect is achieved by directly acting on the superior laryngeal nerve (SLN). In anesthetized and spontaneously breathing rat pups, the following stimulations were applied after intralaryngeally loading 50 μl LA (10 μg/μl) and vehicle for 10 min. Intralaryngeal perfusion of capsaicin (CAP), hydrochloric acid solution (HCl), and distilled water (DW) for 10 s was employed to selectively stimulate local TRPV1, ASIC, and osmotic receptors respectively. Intralaryngeal delivery of air‐puff (AP for 2 s) with peak pressure at ~40 mmHg was utilized to stimulate laryngeal mechanoreceptors. The results showed that CAP, HCl, DW, and AP triggered an immediate apnea with TE prolonged by 24‐, 17‐, 18‐ and 3‐fold respectively. LA per se did not alter baseline ventilation but shortened the CAP‐, HCl‐, and DW‐evoked apneic durations by 75%, 68%, and 54% respectively (P < 0.01) with little effect on the apneic response to AP. To determine the direct effect of LA on the SLN, the latter was bilaterally isolated and pretreated by perilaryngeal LA treatment (10 μg/μl) or vehicle for 20 min. Perilaryngeal LA treatment produced a similar inhibition in CAP‐ and HCl‐induced apneic responses but failed to change DW‐induced apnea. Our results, for the first time, suggest that LA applied on the laryngeal mucosa depresses the stimulatory effects of CAP, HCl, and DW on laryngeal chemoreceptors in which CAP and HCl are capable of directly act on TRPV1 and ASIC of SLN. This finding may extend the therapeutic use of LA to treat a subgroup of SIDS victims with laryngeal disorders and explain, at least partially, the antitussive effect of LA due the critical role of laryngeal sensory afferents in cough initiation. The cellular mechanisms underlying this inhibition are warranted for further investigation.
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NIH HL119683
This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.