Effect of 5-hydroxytryptamine on vagal C-fiber subtypes in guinea pig lungs

Chuaychoo, Benjamas; Lee, Min Goo; Kollárik, Marián; Undem, Bradley J.

doi:10.1016/j.pupt.2004.12.010

Cited by 54 publications

(41 citation statements)

References 21 publications

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“…The activation profile of C-fibers depends on the fiber subtype. For example, in guinea pigs, jugular and nodose C-fibers respond to capsaicin and bradykinin, but only nodose C-fibers respond to serotonin (15), ATP (13), and adenosine (unpublished observations). Differences in chemical activation have also been noted between bronchial and pulmonary C-fibers in dogs and cats (16).…”

Section: Nociceptorsmentioning

confidence: 92%

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

Undem

Kollárik

2005

Proceedings of the American Thoracic Society

104

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Circumstantial evidence supports the hypothesis that the vagal nervous system is dysregulated in chronic obstructive pulmonary disease. This dysregulation can lead to an increased sensitivity of the cough reflex such that the coughing becomes, at times, "nonproductive" or inappropriate. Vagal dysregulation can also lead to an increase in the activity of the parasympathetic reflex control of the airways, which contributes to greater mucus secretion and bronchial smooth muscle contraction. Indirect evidence indicates that lung disease is accompanied by substantive changes to the entire reflex pathways, including enhanced activity of the primary afferent nerves, increases in synaptic efficacy at secondary nerves in the central nervous system, and changes in the autonomic nerve pathways. Drugs aimed at normalizing neuronal activity may, therefore, be beneficial in chronic obstructive pulmonary disease.

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Section: Nociceptorsmentioning

confidence: 92%

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

Undem

Kollárik

2005

Proceedings of the American Thoracic Society

104

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“…The nodose and jugular C-fiber neurons could be readily distinguished pharmacologically. Both subtypes responded directly to capsaicin and bradykinin, but only the nodose C-fibers responded with action potential discharge to ATP and other purinergic P2X receptor-selective agonists, adenosine receptor (A1 and A2A) agonists, and 5-HT3 receptor agonists (5,6,35). In addition, the jugular C-fibers were more apt to express neuropeptides than the nodose C-fibers (35).…”

mentioning

confidence: 99%

P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus

Kwong¹,

Kollárik²,

Nassenstein³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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138

165

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The lungs and esophagus are innervated by sensory neurons with somata in the nodose, jugular, and dorsal root ganglion. These sensory ganglia are derived from embryonic placode (nodose) and neural crest tissues (jugular and dorsal root ganglia; DRG). We addressed the hypothesis that the neuron's embryonic origin (e.g., placode vs. neural crest) plays a greater role in determining particular aspects of its phenotype than the environment in which it innervates (e.g., lungs vs. esophagus). This hypothesis was tested using a combination of extracellular and patchclamp electrophysiology and single-cell RT-PCR from guinea pig neurons. Nodose, but not jugular C-fibers innervating the lungs and esophagus, responded to ␣,␤-methylene ATP with action potential discharge that was sensitive to the P2X3 (P2X2/3) selective receptor antagonist A-317491. The somata of lung-and esophagus-specific sensory fibers were identified using retrograde tracing with a fluorescent dye. Esophageal-and lung-traced neurons from placodal tissue (nodose neurons) responded similarly to ␣,␤-methylene ATP (30 M) with a large sustained inward current, whereas in neurons derived from neural crest tissue (jugular and DRG neurons), the same dose of ␣,␤-methylene ATP resulted in only a transient rapidly inactivating current or no detectable current. It has been shown previously that only activation of P2X2/3 heteromeric receptors produce sustained currents, whereas homomeric P2X3 receptor activation produces a rapidly inactivating current. Consistent with this, single-cell RT-PCR analysis revealed that the nodose ganglion neurons innervating the lungs and esophagus expressed mRNA for P2X2 and P2X3 subunits, whereas the vast majority of jugular and dorsal root ganglia innervating these tissues expressed only P2X3 mRNA with little to no P2X2 mRNA expression. We conclude that the responsiveness of C-fibers innervating the lungs and esophagus to ATP and other purinergic agonists is determined more by their embryonic origin than by the environment of the tissue they ultimately innervate.

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“…For example, our previous studies indicate that nodose but not jugular C-fibers are activated by adenosine A1 or A2 receptor agonists, 5-HT3 receptor agonists, and ATP/purinergic P2X2/3 receptor agonists (10,11,26). As an alternative approach we have used short hairpin RNA (shRNA) technology to modify gene expression in subsets of vagal sensory ganglia neurons (14).…”

mentioning

confidence: 99%

Selective inhibition of vagal afferent nerve pathways regulating cough using Na_v 1.7 shRNA silencing in guinea pig nodose ganglia

Muroi

Ren

Chou

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Selective inhibition of vagal afferent nerve pathways regulating cough using Nav 1.7 shRNA silencing in guinea pig nodose ganglia. Am J Physiol Regul Integr Comp Physiol 304: R1017-R1023, 2013. First published April 10, 2013 doi:10.1152/ajpregu.00028.2013.-Adenoassociated virus delivery systems and short hairpin RNA (shRNA) were used to selectively silence the voltage-gated sodium channel NaV 1.7 in the nodose ganglia of guinea pigs. The cough reflex in these animals was subsequently assessed. NaV 1.7 shRNA was delivered to the majority of nodose ganglia neurons [50 -60% transfection rate determined by green fluorescent protein (GFP) gene cotransfection] and action potential conduction in the nodose vagal nerve fibers, as evaluated using an extracellular recording technique, was markedly and significantly reduced. By contrast, Ͻ5% of neurons in the jugular vagal ganglia neurons were transfected, and action potential conduction in the jugular vagal nerve fibers was unchanged. The control virus (with GFP expression) was without effect on action potential discharge and conduction in either ganglia. In vivo, NaV 1.7 silencing in the nodose ganglia nearly abolished cough evoked by mechanically probing the tracheal mucosa in anesthetized guinea pigs. Stimuli such as capsaicin and bradykinin that are known to stimulate both nodose and jugular C-fibers evoked coughing in conscious animals was unaffected by NaV 1.7 silencing in the nodose ganglia. Nodose C-fiber selective stimuli including adenosine, 2-methyl-5-HT, and ATP all failed to evoke coughing upon aerosol challenge. These results indicate that cough is independently regulated by two vagal afferent nerve subtypes in guinea pigs, with nodose A␦ fibers regulating cough evoked mechanically from the trachea and bradykinin-and capsaicinevoked cough regulated by C-fibers arising from the jugular ganglia. sodium channels; Nav 1.7; vagal reflex; C-fibers; capsaicin STUDIES IN GUINEA PIGS indicate that at least two vagal afferent nerve subtypes can induce coughing upon activation (7,9). In addition to C-fibers, which conduct action potentials at Ͻ2 m/s and are activated by bradykinin and agonists of transient receptor potential vanilloid-1 (TRPV1) and transient receptor potential ankyrin-1 (TRPA1) ion channels, cough is also regulated by neurons that conduct action potentials in the A␦ range (ϳ5 m/s). These small, myelinated afferent nerves are exquisitely sensitive to punctuate mechanical stimulation and rapid decreases in mucosal pH (15, 23) but are insensitive to activators of TRPV1 or TRPA1.The A␦ vagal afferents that regulate cough arise from the nodose ganglia and terminate in the subepithelial extracellular matrix of the extrapulmonary airways (21). C-fibers innervating the guinea pig respiratory tract project from both the nodose and jugular ganglia. The unmyelinated afferents derived from these embryologically distinct ganglia have unique activation profiles and sites of termination in the airways and lungs and thus represent physiologically distinct subtypes (...

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Effect of 5-hydroxytryptamine on vagal C-fiber subtypes in guinea pig lungs

Cited by 54 publications

References 21 publications

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus

Selective inhibition of vagal afferent nerve pathways regulating cough using Na_v 1.7 shRNA silencing in guinea pig nodose ganglia

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