Prostaglandin E<sub>2</sub> Enhances Chemical and Mechanical  Sensitivities of Pulmonary C Fibers in the Rat

Ho, Ching‐Yin; Gu, Qihai; Hong, Ju-Lun; Lee, Lu-Yuan

doi:10.1164/ajrccm.162.2.9910059

Cited by 105 publications

(88 citation statements)

References 26 publications

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“…In addition, PGE 2 infusion also significantly enhanced the C-fiber response to constantpressure lung inflation ( Figure 6). In contrast, the same dose of PGE 2 did not cause any detectable change in the sensitivity of either RARs or slowly adapting pulmonary stretch receptors to lung inflation (34).…”

Section: Excitability Of Airway Afferents Modulated By Inflammatory Mmentioning

confidence: 69%

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Lee

Widdicombe

2001

Environ Health Perspect

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Among the three major types of sensory receptors innervating the airways and lungs, C-fiber endings and rapidly adapting pulmonary receptors (RARs or irritant receptors) are believed to be primarily responsible for eliciting the reflex responses in defending the lungs against inhaled irritants and toxins (1-3). The third type, slowly adapting pulmonary receptors (SARs or stretch receptors), plays an important role in regulating the respiratory volume-timing relationship (4), and is considered to be pure mechanoreceptor and relatively insensitive to chemical irritants. Several recent studies have attempted to uncover the mechanisms underlying the interaction between the pulmonary C fibers and RARs in the overall regulation of the defense reflex responses. Inhalation of cigarette smoke, a common inhaled irritant in human airways, has been shown to elicit irregular breathing pattern, cough reflex, and bronchoconstriction in a number of species including humans (5-9). Although it is believed that most of these responses are mediated through the activation of these two types of vagal afferents, the relative contributions of these two types of afferents to the emergence of these reflex responses are not known. In anesthetized animals (dogs, cats, or rats), spontaneous inhalation of one to two tidal breaths of cigarette smoke into the lungs via a tracheal cannula immediately elicited pulmonary chemoreflexes, characterized by apnea, bradycardia, and hypotension, known to be elicited by activation of pulmonary C fibers (1-3,6). After perineural capsaicin treatment of both cervical vagi to selectively block the conduction of capsaicin-sensitive C fibers, inhaled cigarette smoke no longer evoked any inhibitory effect on breathing (9). Conversely, an augmented inspiration, a reflex effect of activating RARs, was triggered within the first three breaths from the onset of cigarette smoke inhalation in > 85% of the rats studied (Figure 1). When the temperature of the vagus nerve was cooled progressively to 6-7 °C to block the conduction of myelinated afferents, as indicated by the ablation of the apneic response to lung inflation, the augmented breaths evoked by the cigarette smoke inhalation were also abolished (9). Both the apnea and augmented breath evoked by inhaled cigarette smoke were completely abolished by bilateral cervical vagotomy. Similarly, augmented breaths were also elicited when other chemical irritants such as sulfur dioxide (SO 2 ) (9), ammonia (NH 3 ) (9), acrolein (10), and wood smoke (11) were inhaled after the perineural capsaicin treatment of both vagi in anesthetized rats.It is interesting to note that augmented breaths were consistently elicited by inhaled irritants only after the conduction in bronchopulmonary C-fiber afferents are blocked by perineural capsaicin treatment of both vagi but were rarely seen when the same irritants were inhaled in the same animals with intact C fibers (9-11). These results suggest that both vagal bronchopulmonary C-fiber afferents and RARs are stimulated by these inhale...

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Section: Excitability Of Airway Afferents Modulated By Inflammatory Mmentioning

confidence: 69%

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Lee

Widdicombe

2001

Environ Health Perspect

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AbstractProstaglandin E 2 (PGE 2 ) is a prototypical inflammatory mediator that excites and sensitizes cell bodies (Kwong and Lee, 2002; and peripheral nerve terminals (Ho et al 2000) of primary vagal sensory neurons. Nearly all central nerve terminals of vagal afferents are in the nucleus tractus solitarius (NTS), where they operate with a high probability of release (Doyle and Andresen, 2001).

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mentioning

confidence: 99%

Prostaglandin E2 depresses solitary tract-mediated synaptic transmission in the nucleus tractus solitarius

Laaris¹,

Weinreich²

2007

Neuroscience

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Prostaglandin E 2 (PGE 2 ) is a prototypical inflammatory mediator that excites and sensitizes cell bodies (Kwong and Lee, 2002; and peripheral nerve terminals (Ho et al. 2000) of primary vagal sensory neurons. Nearly all central nerve terminals of vagal afferents are in the nucleus tractus solitarius (NTS), where they operate with a high probability of release (Doyle and Andresen, 2001). We studied the effect of PGE 2 on synaptic transmission between tractus solitarius afferent nerve terminals and the second order NTS neurons in brain stem slices of Sprague Dawley rats. Whole-cell patch recording in voltage clamp mode was used to study evoked excitatory postsynaptic glutamatergic currents (evEPSCs) from NTS neurons elicited by electrical stimulation of the solitary tract (ST). In 34 neurons, bath applied PGE 2 (200 nM) decreased the evEPSC amplitude by 49 ± 5 %. In 22 neurons, however, PGE 2 had no effect. We also tested 15 NTS neurons for capsaicin sensitivity. Seven neurons generated evEPSCs that were equally unaffected by PGE 2 and capsaicin. Conversely, evEPSCs of the other 8 neurons, which were PGE 2 -responsive, were abolished by 200 nM capsaicin. Furthermore, the PGE 2-induced depression of evEPSCs was associated with an increase in the paired pulse ratio and a decrease in both the frequency and amplitude of the spontaneous excitatory postsynaptic currents (sEPSCs) and TTX-independent spontaneous miniature excitatory postsynaptic currents (mEPSCs). These results suggest that PGE 2 acts both presynaptically on nerve terminals and postsynaptically on NTS neurons to reduce glutamatergic responses. KeywordsGlutamate; AMPA receptors; Presynaptic; Postsynaptic Many neurons in the nucleus of the tractus solitarius (NTS) receive nerve terminals whose axons arise from cell bodies of vagal primary afferent neurons located in the nodose and jugular vagal ganglia. These primary vagal afferents convey diverse sensory information from a variety of receptors located in cardiovascular, respiratory, gastrointestinal and other organs to the NTS neurons in the medulla (Contreras, 1982). Thus, the first monosynaptic contact for myelinated A-type and unmyelinated C-type axons of primary vagal afferent fibers are the second-order neurons in the NTS. These fibers reach second-order NTS neurons via the solitary tract (Doyle Corresponding author: Nora Laaris, Department Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, Tel: (410) 706-1409, Fax: (410) 706-0032, e-mail: nlaar001@umaryland.edu. Section Editor: Dr. Yoland Smith, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its fin...

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“…PGE 2 is known to induce airway hypersensitivity; for example, inhalation of aerosolized PGE 2 elicits cough and retrosternal soreness (Costello et al, 1985), and enhances the sensitivity of the cough reflex response to inhaled capsaicin in humans (Chaudry et al, 1989). Indeed, an earlier study in our lab has shown that PGE 2 can elevate the sensitivity of pulmonary C-fiber afferents (Ho et al, 2000). Studies in an isolated pulmonary nodose/jugular neuron preparation further revealed that the sensitizing effect involves the intracellular cAMP/PKA signaling pathway, which is presumably triggered by activation of EP 2 and EP 4 prostanoid receptors expressed in these neurons (Kwong and Lee, 2002;Gu et al, 2003).…”

Section: Introductionmentioning

confidence: 84%

Prostaglandin E2 enhances the sensitizing effect of hyperthermia on pulmonary C-fibers in rats

Zhang

Lee

2007

Respiratory Physiology & Neurobiology

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This study was carried out to investigate whether the pulmonary C-fiber hypersensitivity induced by hyperthermia is altered by prostaglandin E 2 (PGE 2 ). Single-unit afferent activities of pulmonary C-fibers were recorded in anesthetized, artificially ventilated rats when the intrathoracic temperature (T it ) was maintained at normal (N; ~36°C) and hyperthermia levels (H; ~41°C) by perfusion of heated saline into the thoracic chamber for 3 min. After ~20 min of recovery, the fiber activities were recorded again during infusion of PGE 2 at both N and H levels of T it . Our study showed: 1) The baseline fiber activity and responses to lung inflation, right atrial injection of capsaicin and adenosine were all increased by increasing T it from N to H, and these hyperthermia-induced increases in sensitivities were also significantly augmented by PGE 2 . 2) These enhanced sensitivities induced by PGE 2 were abolished by pretreatment with AH6809 and AH23848, selective antagonists of EP 2 and EP 4 prostanoid receptors, respectively. In conclusion, the hyperthermia-induced hypersensitivity of vagal pulmonary C-fibers is potentiated by PGE 2 , and this effect is mediated through activation of EP 2 and EP 4 prostanoid receptors.

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Prostaglandin E₂ Enhances Chemical and Mechanical Sensitivities of Pulmonary C Fibers in the Rat

Cited by 105 publications

References 26 publications

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Prostaglandin E2 depresses solitary tract-mediated synaptic transmission in the nucleus tractus solitarius

Prostaglandin E2 enhances the sensitizing effect of hyperthermia on pulmonary C-fibers in rats

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Prostaglandin E2 Enhances Chemical and Mechanical Sensitivities of Pulmonary C Fibers in the Rat

Cited by 105 publications

References 26 publications

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Prostaglandin E2 depresses solitary tract-mediated synaptic transmission in the nucleus tractus solitarius

Prostaglandin E2 enhances the sensitizing effect of hyperthermia on pulmonary C-fibers in rats

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Prostaglandin E₂ Enhances Chemical and Mechanical Sensitivities of Pulmonary C Fibers in the Rat