Abstract

5-hydroxytryptamine (5-HT) is an inflammatory mediator known to be released in lung. Capsaicin-sensitive lung vagal (CSLV) afferents function as a primary sensor for detecting chemical stimuli and produce consequent reflexes during lung inflammation. To characterize the effect of 5-HT on CSLV afferents, responses of cardiorespiratory reflexes and single-unit C-fiber afferents to right-atrial injections of 5-HT were investigated in anesthetized Sprague-Dawley rats. Bolus injection of 5-HT (8 μg/kg) caused an immediate augmented breath and apnea, accompanied by hypotension and bradycardia. These initial responses were then followed by a brief pressor response and a more sustained depressor response. After a perineural treatment of both cervical vagi with capsaicin to block the conduction of C fibers, 5-HT still triggered the augmented breath, but no longer evoked the apnea, bradycardia and hypotension, indicating an involvement of C-fiber activation. The remaining augmented breath induced by 5-HT after perineural capsaicin treatment was totally eliminated by vagotomy. To further study the effect of 5-HT on CSLV afferents, activities arising from these afferents were determined using the single-fiber recording technique. Right-atrial injection of 5-HT evoked an intense discharge in CSLV afferents in a dose-dependent manner. The highest dose of 5-HT (16 μg/kg) activated 79% (19/24) of CSLV afferents which were also sensitive to capsaicin (0.8 μg/kg). The pretreatment of tropisetron, a selective antagonist of the 5-HT3 receptor, completely blocked CSLV-afferents stimulation induced by 5-HT but did not affect that by capsaicin. Furthermore, a similar afferent response of CSLV afferents was mimicked by phenylbiguanide, a selective agonist of the 5-HT3 receptor. In isolated rat lung vagal C neurons, 5-HT induced intense calcium transients in a dose-dependent manner. The highest concentration (3 μM) of 5-HT activated 67% (18/27) of the CSLV neurons. The 5-HT-induced response was totally abolished by pretreatment of tropisetron. In conclusion, 5-HT exerts an intense stimulatory effect on lung C-fiber terminals mediated through an activation of the 5-HT3 receptor, which may contribute to the airway hypersensitivity under lung inflammation.

Document Type

Article

Publication Date

5-28-2019

Notes/Citation Information

Published in Frontiers in Physiology, v. 10, article 642, p. 1-12.

Copyright © 2019 Hsu, Ruan, Lee and Lin.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Digital Object Identifier (DOI)

https://doi.org/10.3389/fphys.2019.00642

Funding Information

The study was supported in part by grants TMU105-AE1-B17 (C-CH), MOST105-2320-B-038-070-MY2 (C-CH), DP2-108-21121-01-T-01-03 (C-CH), MOST104-2320-B-038-029- (YSL), NIH HL96914 (L-YL), and NIH AI123832 (L-YL).

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