Functional and morphological organization of the nucleus tractus solitarius in the fictive cough reflex of guinea pigs

Ohi, Yoshiaki; Yamazaki, Hiromi; Takeda, Ryuji; Haji, Akira

doi:10.1016/j.neures.2005.06.016

Cited by 36 publications

(38 citation statements)

References 37 publications

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“…Inhibiting it at any site of the arc can be expected to cause antitussive effect. 11,15) In general, opioids are thought to suppress preferentially synaptic transmissions in the cough/respiratory neuron network 5,11) and NMDA mechanisms may play some roles in the gating mechanism which integrates the cough-related information coming from the NTS relay neurons and sends the gated signal to the cough/respiratory pattern generator. 10,16) The present results propose another possible site of action where both opioid and NMDA ligands act onto the postsynaptic receptors located in LMNs and modulate the motoneuron excitability.…”

Section: Discussionmentioning

confidence: 99%

“…10,16) The present results propose another possible site of action where both opioid and NMDA ligands act onto the postsynaptic receptors located in LMNs and modulate the motoneuron excitability. Therefore, it is speculated that activation of m-opioid receptors 5,6,17) or blockade of NMDA receptors 7,10) may be capable of decreasing the cricothyroid muscle tone to some extent, leading to suppression of cough production. 11,17) It has been reported in the ventrolateral periaqueductal gray that frequent colocalization of m-opioid and NMDA receptors was shown within dendrites and suggested the modulation on the antinociception.…”

Section: Discussionmentioning

confidence: 99%

“…5,10,11) However, whether such mechanisms are directly involved in cough-related efferent signals is not clarified yet. The present study focused on modulation of the activity of laryngeal motoneurons (LMNs) providing efferent fibers to the SLN by m-opioid and NMDA mechanisms.…”

Section: )mentioning

confidence: 99%

“…It has been reported that opioids including morphine, codeine, endomolphin-1 and 2 inhibit occurrence of cough reflex in cats, 3) guinea pigs 4,5) and mice. 6) Moreover, blockade of the N-methyl-D-aspartate (NMDA) receptors effectively suppresses cough reflex in rats, 7) rabbits 8,9) and cats.…”

mentioning

confidence: 99%

“…10) These results suggest that m-opioid and NMDA receptors play important roles in generation of cough reflex, by which these mechanisms act in the central regions such as the nucleus tractus solitarius (NTS) and the cough/respiratory neuron network. 5,10,11) However, whether such mechanisms are directly involved in cough-related efferent signals is not clarified yet. The present study focused on modulation of the activity of laryngeal motoneurons (LMNs) providing efferent fibers to the SLN by m-opioid and NMDA mechanisms.…”

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confidence: 99%

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.MU.-Opioid and N-Methyl-D-aspartate Receptors Are Localized at Laryngeal Motoneurons of Guinea Pigs

Yamazaki

Ohi

Haji

2009

Biological & Pharmaceutical Bulletin

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Behavior of coughing is produced by combination of a series of laryngeal and respiratory muscle contraction. Movements of laryngeal muscles are governed by laryngeal motoneurons via two main efferent nerves.1) The superior laryngeal nerve (SLN) innervates the cricothyroid muscle, and the recurrent laryngeal nerve innervates the posterior cricoarytenoid, thyroarytenoid, lateral cricoarytenoid and interarytenoid muscles. The cricothyroid muscle contracts in concert with the posterior cricoarytenoid muscle and can facilitate laryngeal opening during coughing. 1,2)It has been reported that opioids including morphine, codeine, endomolphin-1 and 2 inhibit occurrence of cough reflex in cats, 3) guinea pigs 4,5) and mice. 6) Moreover, blockade of the N-methyl-D-aspartate (NMDA) receptors effectively suppresses cough reflex in rats, 7) rabbits 8,9) and cats. 10)These results suggest that m-opioid and NMDA receptors play important roles in generation of cough reflex, by which these mechanisms act in the central regions such as the nucleus tractus solitarius (NTS) and the cough/respiratory neuron network. 5,10,11) However, whether such mechanisms are directly involved in cough-related efferent signals is not clarified yet. The present study focused on modulation of the activity of laryngeal motoneurons (LMNs) providing efferent fibers to the SLN by m-opioid and NMDA mechanisms. The LMNs were identified immunohistochemically by application of the fluorescent wheat-germ agglutinin (WGA) conjugate, and then double staining was undertaken with antibodies to either m-opioid or NMDA receptors. MATERIALS AND METHODS Preparation of SlicesThis study was conducted in accordance with Guiding Principles for the Care and Use of Laboratory Animals approved by The Japanese Pharmacological Society. Eight guinea pigs (Hartley strain, 400-700 g body weight) were anesthetized with ketamine and xylazine (80 and 8 mg/kg, intramuscularly). The right SLN was dissected free from the surrounding tissue and the proximal central cut end of the nerve was soaked in 3 ml of 5% WGA-Fl (WGA-Alexa Fluor 488 conjugate, Molecular Probes, Eugene, OR, U.S.A.) in saline for 90 min. After 24 to 48 h, the animals were anesthetized deeply with ketamine and xylazine, and perfused transcardially with 200 ml of physiological saline containing heparin (5 U/ml), followed by 150 ml of 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4). The brainstem was dissected, post-fixed for 60 min, and placed in 10 mM phosphate buffered saline (PBS, pH 7.4) at 4°C. Serial coronal slices (50 mm thickness) were cut with a vibratome.Immunoreactivity of m m-Opioid and NMDA Receptors Free floating sections were incubated in PBS containing 0.2% Tween 20 for 20 min at room temperature, washed three times with PBS for 5 min and incubated in a blocking buffer containing 10% of goat normal serum diluted with PBS solution for 10 min. Tissue sections were then incubated at 4°C for 18 h with following a primary antibody: either rabbit polyclonal antibody raised against the 3rd extracellula...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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.MU.-Opioid and N-Methyl-D-aspartate Receptors Are Localized at Laryngeal Motoneurons of Guinea Pigs

Yamazaki

Ohi

Haji

2009

Biological & Pharmaceutical Bulletin

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Sensory Nerves and Airway Irritability

Canning¹,

Spina

2009

Sensory Nerves

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The lung, like many other organs, is innervated by a variety of sensory nerves and by nerves of the parasympathetic and sympathetic nervous systems that regulate the function of cells within the respiratory tract. Activation of sensory nerves by both mechanical and chemical stimuli elicits a number of defensive reflexes, including cough, altered breathing pattern, and altered autonomic drive, which are important for normal lung homeostasis. However, diseases that afflict the lung are associated with altered reflexes, resulting in a variety of symptoms, including increased cough, dyspnea, airways obstruction, and bronchial hyperresponsiveness. This review summarizes the current knowledge concerning the physiological role of different sensory nerve subtypes that innervate the lung, the factors which lead to their activation, and pharmacological approaches that have been used to interrogate the function of these nerves. This information may potentially facilitate the identification of novel drug targets for the treatment of respiratory disorders such as cough, asthma, and chronic obstructive pulmonary disease.

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Central Mechanisms II: Pharmacology of Brainstem Pathways

Bolser

2009

Pharmacology and Therapeutics of Cough

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Following systemic administration, centrally acting antitussive drugs are generally assumed to act in the brainstem to inhibit cough. However, recent work in humans has raised the possibility of suprapontine sites of action for cough suppressants. For drugs that may act in the brainstem, the specific locations, types of neurones affected, and receptor specificities of the compounds represent important issues regarding their cough-suppressant actions. Two medullary areas that have received the most attention regarding the actions of antitussive drugs are the nucleus of the tractus solitarius (NTS) and the caudal ventrolateral respiratory column. Studies that have implicated these two medullary areas have employed both microinjection and in vitro recording methods to control the location of action of the antitussive drugs. Other brainstem regions contain neurones that participate in the production of cough and could represent potential sites of action of antitussive drugs. These regions include the raphe nuclei, pontine nuclei, and rostral ventrolateral medulla. Specific receptor subtypes have been associated with the suppression of cough at central sites, including 5-HT1A, opioid (μ, κ, and δ), GABA-B, tachykinin neurokinin-1 (NK-1) and neurokinin-2, non-opioid (NOP-1), cannabinoid, dopaminergic, and sigma receptors. Aside from tachykinin NK-1 receptors in the NTS, relatively little is known regarding the receptor specificity of putative antitussive drugs in particular brainstem regions. Our understanding of the mechanisms of action of antitussive drugs would be significantly advanced by further work in this area.

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Functional and morphological organization of the nucleus tractus solitarius in the fictive cough reflex of guinea pigs

Cited by 36 publications

References 37 publications

.MU.-Opioid and N-Methyl-D-aspartate Receptors Are Localized at Laryngeal Motoneurons of Guinea Pigs

.MU.-Opioid and N-Methyl-D-aspartate Receptors Are Localized at Laryngeal Motoneurons of Guinea Pigs

Sensory Nerves and Airway Irritability

Central Mechanisms II: Pharmacology of Brainstem Pathways

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