Nitric oxide synthase in vagal sensory and sympathetic neurons innervating the guinea-pig trachea

doi:10.1016/0165-1838(95)00085-2

Journal of the Autonomic Nervous System

Volume 56, Issue 3, 5 January 1996, Pages 157-160

Journal of the Auton...

https://doi.org/10.1016/0165-1838(95)00085-2 Get rights and content

Abstract

Sympathetic (stellate and superior cervical ganglion) and sensory vagal (nodose and jugular ganglion) neurons innervating the guinea-pig trachea were labelled using a retrograde neuronal tracer (Fast Blue) and tested for immunoreactivity to nitric oxide synthase (NOS) and either tyrosine hydroxylase (TH; sympathetic ganglia) or substance P (SP; vagal afferent neurons). Approx. 3% of the sympathetic neurons innervating the trachea were NOS-positive. These neurons belonged to the non-catecholaminergic phenotype. Amongst the retrogradely labelled neurons in the vagal sensory ganglia, 5–10% of retrogradely labelled neurons in the nodose (inferior vagal) ganglion, and 10–20% of those in the jugular (superior vagal) ganglion were NOS-immunoreactive. All NOS-positive vagal afferent neurons labelled with retrograde tracer were negative for substance P. Accordingly, the results of these studies provide evidence that portions of the sympathetic and sensory innervation of the guinea-pig trachea is provided by NOS-immunoreactive neurons.

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Sensory neurons in the human jugular ganglion
2020, Tissue and Cell
Citation Excerpt :
These data may suggest co-expression of the TRPV1 and TRPV2 in the human vagal sensory system. On the other hand, SP- and CGRP-containing neurons are numerous within the jugular ganglion but not the nodose ganglion of the mouse, rat and guinea pig (Fischer and Hoffmann, 1996; Fischer et al., 1996; Grunditz et al., 1986; Hayakawa et al., 2014; Helke and Rabchevsky, 1991; Ichikawa et al., 1993). Therefore, it is likely that the cranial regions are probably main targets of SP- and CGRP-containing neurons in the human and rodent vagal nervous system.
The jugular ganglion (JG) contains sensory neurons of the vagus nerve which innervate somatic and visceral structures in cranial and cervical regions. In this study, the number of sensory neurons in the human JG was investigated. And, the morphology of sensory neurons in the human JG and nodose ganglion (NG) was compared. The estimated number of JG neurons was 2721.8–9301.1 (average number of sensory neurons ± S.D. = 7975.1 ± 3312.8). There was no significant difference in sizes of the neuronal cell body and nucleus within the JG (cell body, 1128.8 ± 99.7 μ m²; nucleus, 127.7 ± 20.8 μ m²) and NG (cell body, 963.8 ± 225.7 μ m²; nucleus, 123.2 ± 32.3 μ m²). These findings indicate that most of sensory neurons show the similar morphology in the JG and NG. Our immunohistochemical method also demonstrated the distribution of ion channels, neurotransmitter agents and calcium-binding proteins in the human JG. Numerous JG neurons were immunoreactive for transient receptor potential cation channel subfamily V member 1 (TRPV1, mean ± SD = 19.9 ± 11.5 %) and calcitonin gene-related peptide (CGRP, 28.4 ± 6.7 %). A moderate number of JG neurons contained TRPV2 (12.0 ± 4.7 %), substance P (SP, 15.7 ± 6.9 %) and secreted protein, acidic and rich in cysteine-like 1 (SPARCL1, 14.6 ± 7.4 %). A few JG neurons had vesicular glutamate transporter 2 (VGLUT2, 5.6 ± 2.9 %) and parvalbumin (PV, 2.3 ± 1.4 %). SP- and TRPV2-containing JG neurons had mainly small and medium-sized cell bodies, respectively. TRPV1- and VGLUT2- containing JG neurons were small to medium-sized. CGRP- and SPARCL1-containing JG neurons were of various cell body sizes. Sensory neurons in the human JG were mostly free of vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH) and neuropeptide Y (NPY). In the external auditory canal skin, subepithelial nerve fibers contained TRPV1, TRPV2, SP, CGRP and VGLUT2. Perivascular nerve fibers also had TRPV1, TRPV2, SP, CGRP, VIP, NPY and TH. However, PV- and SPARCL1-containing nerve endings could not be seen in the external auditory canal. It is likely that sensory neurons in the human JG can transduce nociceptive and mechanoreceptive information from the external auditory canal. Theses neurons may be also associated with neurogenic inflammation in the external auditory canal and ear-cough reflex through the vagus nerve.
Immunohistochemical characterization of the porcine nodose ganglion
2013, Acta Histochemica
Citation Excerpt :
Unfortunately available data have not shown the exact percentage of the nitrergic neurons in the rat GN. The retrograde study indicated only that approximately 5–10% of tracheal afferent neurons, whose perikarya are located in GN, contain NOS (Fischer et al., 1996). Nitric oxide owing to its gaseous nature and high permeability is able to diffuse as a sphere up to 300 μm.
This study reports for the first time the presence of several biologically active substances in the nodose ganglion of immature female pigs. The expression and distribution pattern of the studied substances was examined using a double-labeling immunofluorescence technique. In order to visualize the entire population of the ganglionic cell bodies, PGP 9.5, the pan-neuronal marker was used. The distribution and relative proportion of immunolocalized substance P, calcitonin gene related peptide, neuronal isoform of nitric oxide synthase and galanin in perikarya were evaluated. Quantitative analysis of the nodose ganglion neurons revealed that 16.187% (±1.22) of the immunoreactive PGP 9.5 was localized in the perikarya of the left-side ganglion whereas 14.234% (±3.63) of the right-side ganglion neurons expressed substance P, respectively. Accordingly, the proportion of the perikarya with calcitonin gene related peptide ranged from 12.667% (±2.66) for the left ganglion compared with 14.875% (±2.33) for the right one. With regard to the neuronal isoform of the nitric oxide synthase expression, our study revealed a population of 18.703% (±2.50) in the left and 13.336% (±1.25) in the right ganglion, respectively. The immunoreactivity for galanin was found in a relatively small population of neurons of the left nodose ganglion, where galanin-immunoreactive perikarya constituted 1.163% (±1.26), while in the contralateral ganglion 0.865% (±0.32) of total perikarya. No nerve fibers immunopositive for the above studied substances were encountered.
Reactive nitrogen species in the respiratory tract
2006, European Journal of Pharmacology
Endogenous Nitric Oxide (NO) plays a key role in the physiological regulation of airway functions. In response to various stimuli activated inflammatory cells (e.g., eosinophils and neutrophils) generate oxidants (“oxidative stress”) which in conjunction with exaggerated enzymatic release of NO and augmented NO metabolites produce the formation of strong oxidizing reactive nitrogen species, such as peroxynitrite, in various airway diseases including asthma, chronic obstructive pulmonary diseases (COPD), cystic fibrosis and acute respiratory distress syndrome (ARDS). Reactive nitrogen species provoke amplification of inflammatory processes in the airways and lung parenchyma causing DNA damage, inhibition of mitochondrial respiration, protein dysfunction and cell damage (“nitrosative stress”). These effects alter respiratory homeostasis (such as bronchomotor tone and pulmonary surfactant activity) and the long-term persistence of “nitrosative stress” may contribute to the progressive deterioration of pulmonary functions leading to respiratory failure.
Recent studies showing that protein nitration can be dynamic and reversible (“denitration mechanisms”) open new horizons in the treatment of chronic respiratory diseases affected by the deleterious actions of “nitrosative stress”.
Expression of substance P and nitric oxide synthase in vagal sensory neurons innervating the mouse airways
2005, Regulatory Peptides
Airway sensory nerves have the capacity to release neuromediators such as substance P and nitric oxide to control airway functions. The aim of the present study was to investigate substance P and neuronal nitric oxide synthase (NOS-1) expression in airway-specific sensory neurons.
Airway-projecting neurons in the jugular-nodose ganglia were investigated for NOS-1 and substance P expression by neuronal tracing and double-labelling immunoreactivity.
Of the Fast blue labelled neurons, 14.6±1.8% (mean±S.E.M.) were immunoreactive only for NOS-1, 3.0±0.3% for NOS-1 and substance P, 2.7±0.3% only for substance P, and 79.7±1.7% of the labelled neurons were nonimmunoreactive for substance P or NOS-1 but were partly positive for I-B4-lectin-binding. Fast blue labelled NOS and/or substance P-positive neurons were small to medium sized (<20μm).
Based on the expression of substance P and nitric oxide synthase in airway neurons, the present study suggests that there may be substance P and NO biosynthesis and release following a peripheral activation of the afferents, there could be a triggering of substance P and NO-mediated phenomena, including those related to airway inflammation, such as plasma extravasation and vasodilatation.
Expression of substance P and vanilloid receptor (VR1) in trigeminal sensory neurons projecting to the mouse nasal mucosa
2003, Neuropeptides
Substance P and neurokinin A (NKA) have potent pro-inflammatory effects in the airways. The release of these neuropeptides from primary afferent (sensory) nerve endings to various stimuli is considered to be induced by activation of the capsaicin (vanilloid) receptor (VR1). In this study, retrograde neuronal tracing studies were combined with immunohistochemistry for VR1 and substance P to investigate the occurrence and distribution of substance P and VR1 receptor expression in mouse trigeminal neurons that were identified by retrograde labeling with Fast blue dye from the nasal mucosa. Fast blue signaling was observed in mucosa layers of the right nasal cavity and in sensory trigeminal neurons close to the division of the ophthalmic and maxillary nerve. Expression patterns of VR1 and substance P were found with different frequencies: 11.3 ± 1.2% (mean ± SEM) were immunoreactive for VR1, 4.9 ± 1.1% for VR1 and SP, and 6.4 ± 1.3% only for VR1 but not for SP. These VR1-positive neurons were partly binding to lectin I-B4, indicating VR1-expression in non-peptidergic upper airway C-fibers. In conclusion, based on the extent of SP and VR1 co-localization in nasal afferent neurons, the present study suggests that, following a peripheral activation of the VR1 receptor on SP afferents, there could be a triggering of SP-mediated phenomena, including those related to inflammation, such as plasma extravasation.
Chemical stimulation of vagal afferent neurons and sympathetic vasomotor tone
2003, Brain Research Reviews
Citation Excerpt :
Rat esophageal vagal afferents contain calretinin and calbindin but not CGRP or NADPH diaphorase [60]. A small percentage of guinea pig tracheal vagal afferents contained nitric oxide synthase (NOS) immunoreactivity [66]. Substance P was not co-localized with NOS in these neurons.
Vagal afferents innervate a diverse range of structures of the thoracic and abdominal viscera. While a proportion of these afferents function as mechanoreceptors and respond to changes in intramural tension within the structures that they innervate, many also sense a broad range of chemical substances ranging from peptides, sugars and lipids present in the intraluminal contents of the gastrointestinal tract, as well as tissue prostanoids, cytokines and monoamines in the cardiopulmonary circulation. This review examines the effects of chemical stimulation of vagal afferents on circulatory and sympathetic vasomotor function. Notably, the von Bezold–Jarisch reflex is a cardiorespiratory reflex produced by chemical activation of cardiopulmonary vagal afferents. Classical stimulants of the von Bezold–Jarisch reflex include the Veratrum alkaloids and 5-HT₃ receptor agonists. Atrial natriuretic peptides are agents which also produce a von Bezold–Jarisch reflex-like response or a sensitisation of this reflex via an action on vagal afferents. Cholecystokinin (CCK) activates abdominal visceral vagal afferents, which apart from a clear role in mediation of satiety, also produces selective sympathetic vasomotor inhibition probably by inhibition of sub-groups of presympathetic vasomotor neurons of the rostral ventrolateral medulla. These actions of CCK may constitute a novel gastrointestinal-cardiovascular reflex. The afferent vagus transmits a diverse array of signals to the central nervous system, influencing sympathetic vasomotor and cardiomotor function, gastrointestinal function, neuroimmune function and endocrine function.

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Research paperNitric oxide synthase in vagal sensory and sympathetic neurons innervating the guinea-pig trachea

Abstract

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Research paper
Nitric oxide synthase in vagal sensory and sympathetic neurons innervating the guinea-pig trachea