scholarly journals Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit

2014 ◽  
Vol 307 (11) ◽  
pp. R1358-R1367 ◽  
Author(s):  
Donatella Mutolo ◽  
Elenia Cinelli ◽  
Fulvia Bongianni ◽  
Tito Pantaleo
Keyword(s):  
Inhibitory Control ◽  
Tracheobronchial Tree ◽  
Nucleus Tractus Solitarii ◽  
Cycle Duration ◽  
Cough Reflex ◽  
Central Processing ◽  
Airway Mucosa ◽  
Galanin Receptors ◽  
Spontaneously Breathing ◽  
Stimulation Of

The caudal nucleus tractus solitarii (NTS) is the main central station of cough-related afferents and a strategic site for the modulation of the cough reflex. The similarities between the characteristics of central processing of nociceptive and cough-related inputs led us to hypothesize that galanin, a neuropeptide implicated in the control of pain, could also be involved in the regulation of the cough reflex at the level of the NTS, where galanin receptors have been found. We investigated the effects of galanin and galnon, a nonpeptide agonist at galanin receptors, on cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. Drugs were microinjected (30–50 nl) into the caudal NTS of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Galnon antitussive effects on cough responses to the mechanical stimulation of the airway mucosa via a custom-built device were also investigated. Bilateral microinjections of 1 mM galanin markedly decreased cough number, peak abdominal activity, and increased cough-related total cycle duration. Bilateral microinjections of 1 mM galnon induced mild depressant effects on cough, whereas bilateral microinjections of 10 mM galnon caused marked antitussive effects consistent with those produced by galanin. Galnon effects were confirmed by using the cough-inducing device. The results indicate that galanin receptors play a role in the inhibitory control of the cough reflex at the level of the caudal NTS and provide hints for the development of novel antitussive strategies.

Suppression of the cough reflex by inhibition of ERK1/2 activation in the caudal nucleus tractus solitarii of the rabbit

2012 ◽  
Vol 302 (8) ◽  
pp. R976-R983 ◽  
Author(s):  
Donatella Mutolo ◽  
Fulvia Bongianni ◽  
Elenia Cinelli ◽  
Maria Grazia Giovannini ◽  
Tito Pantaleo
Keyword(s):  
Tracheobronchial Tree ◽  
Nucleus Tractus Solitarii ◽  
Cough Reflex ◽  
Central Processing ◽  
A Site ◽  
Short Time ◽  
Spontaneously Breathing ◽  
Antitussive Agents ◽  
Inactive Analog

The caudal nucleus tractus solitarii (cNTS), the predominant site of termination of cough-related afferents, has been shown to be a site of action of some centrally acting antitussive agents. A role of ERK1/2 has been suggested in acute central processing of nociceptive inputs. Because pain and cough share similar features, we investigated whether ERK1/2 activation could also be involved in the central transduction of tussive inputs. For this purpose, we undertook the present research on pentobarbital sodium-anesthetized, spontaneously breathing rabbits by using microinjections (30–50 nl) of an inhibitor of ERK1/2 activation (U0126) into the cNTS. Bilateral microinjections of 25 mM U0126 caused rapid and reversible reductions in the cough responses induced by both mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. In particular, the cough number and peak abdominal activity decreased. Bilateral microinjections of 50 mM U0126 completely suppressed the cough reflex without affecting the Breuer-Hering inflation reflex, the pulmonary chemoreflex, and the sneeze reflex. These U0126-induced effects were, to a large extent, reversible. Bilateral microinjections of 50 mM U0124, the inactive analog of U0126, at the same cNTS sites had no effect. This is the first study that provides evidence that ERK1/2 activation within the cNTS is required for the mediation of cough reflex responses in the anesthetized rabbit. These results suggest a role for ERK1/2 in the observed effects via nontranscriptional mechanisms, given the short time involved. They also may provide hints for the development of novel antitussive strategies.

scholarly journals GABAA- and glycine-mediated inhibitory modulation of the cough reflex in the caudal nucleus tractus solitarii of the rabbit

2016 ◽  
Vol 311 (3) ◽  
pp. L570-L580 ◽  
Author(s):  
Elenia Cinelli ◽  
Ludovica Iovino ◽  
Fulvia Bongianni ◽  
Tito Pantaleo ◽  
Donatella Mutolo
Keyword(s):  
Tracheobronchial Tree ◽  
Second Order ◽  
Nucleus Tractus Solitarii ◽  
Glycine Receptors ◽  
Cough Reflex ◽  
C Fibers ◽  
Arterial Blood ◽  
Inhibitory Modulation ◽  
Spontaneously Breathing

Cough-related sensory inputs from rapidly adapting receptors (RARs) and C fibers are processed by second-order neurons mainly located in the caudal nucleus tractus solitarii (NTS). Both GABAA and glycine receptors have been proven to be involved in the inhibitory control of second-order cells receiving RAR projections. We investigated the role of these receptors within the caudal NTS in the modulation of the cough reflex induced by either mechanical or chemical stimulation of the tracheobronchial tree in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections (30–50 nl) of the receptor antagonists bicuculline and strychnine as well as of the receptor agonists muscimol and glycine were performed. Bicuculline (0.1 mM) and strychnine (1 mM) caused decreases in peak abdominal activity and marked increases in respiratory frequency due to decreases in both inspiratory time (Ti) and expiratory time (Te), without concomitant changes in arterial blood pressure. Noticeably, these microinjections induced potentiation of the cough reflex consisting of increases in the cough number associated with decreases either in cough-related Ti after bicuculline or in both cough-related Ti and Te after strychnine. The effects caused by muscimol (0.1 mM) and glycine (10 mM) were in the opposite direction to those produced by the corresponding antagonists. The results show that both GABAA and glycine receptors within the caudal NTS mediate a potent inhibitory modulation of the pattern of breathing and cough reflex responses. They strongly suggest that disinhibition is one important mechanism underlying cough regulation and possibly provide new hints for novel effective antitussive strategies.

Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit

2008 ◽  
Vol 295 (1) ◽  
pp. R243-R251 ◽  
Author(s):  
Donatella Mutolo ◽  
Fulvia Bongianni ◽  
Elenia Cinelli ◽  
Giovanni A. Fontana ◽  
Tito Pantaleo
Keyword(s):  
Substance P ◽  
Receptor Antagonist ◽  
Nucleus Tractus Solitarii ◽  
Cycle Duration ◽  
Cough Reflex ◽  
Caudal Portion ◽  
Tracheal Pressure ◽  
Site Of Action ◽  
A Site ◽  
Antitussive Agents

We have previously shown that ionotropic glutamate receptors in the caudal portion of the nucleus tractus solitarii (NTS), especially in the commissural NTS, play a prominent role in the mediation of tracheobronchial cough and that substance P potentiates this reflex. This NTS region could be a site of action of some centrally acting antitussive agents and a component of a drug-sensitive gating mechanism of cough. To address these issues, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30–50 nl) of centrally acting antitussive drugs into the caudal NTS of pentobarbitone-anesthetized, spontaneously breathing rabbits. [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and baclofen decreased baseline respiratory frequency because of increases in the inspiratory time only at the higher concentration employed (5 mM and 1 mM, respectively). DAMGO (0.5 mM) and baclofen (0.1 mM) significantly decreased cough number, peak abdominal activity, peak tracheal pressure, and increased cough-related total cycle duration. At the higher concentrations, these agents suppressed the cough reflex. The effects of these two drugs were counteracted by specific antagonists (10 mM naloxone and 25 mM CGP-35348, respectively). The neurokinin-1 (NK1) receptor antagonist CP-99,994 (10 mM) abolished cough responses, whereas the NK2 receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the caudal NTS is a site of action of some centrally acting drugs and a likely component of a neural system involved in cough regulation. A crucial role of substance P release in the mediation of reflex cough is also suggested.

scholarly journals Microinjection of codeine into the region of the caudal ventral respiratory column suppresses cough in anesthetized cats

2010 ◽  
Vol 108 (4) ◽  
pp. 858-865 ◽  
Author(s):  
Ivan Poliacek ◽  
Cheng Wang ◽  
Lu Wen-Chi Corrie ◽  
Melanie J. Rose ◽  
Donald C. Bolser
Keyword(s):  
Mechanical Stimulation ◽  
Motor Response ◽  
Esophageal Pressure ◽  
Transversus Abdominis ◽  
Homocysteic Acid ◽  
Cough Reflex ◽  
Posterior Cricoarytenoid ◽  
Spontaneously Breathing ◽  
The Brain ◽  
Stimulation Of

We investigated the influence of microinjection of codeine into the caudal ventral respiratory column (cVRC) on the cough reflex. Experiments were performed on 36 anesthetized spontaneously breathing cats. Electromyograms (EMGs) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. The unilateral microinjection of codeine (3.3 mM, 20–32 nl) in the cVRC reduced cough number by 29% ( P < 0.01) and expiratory cough amplitudes of esophageal pressure by 33% ( P < 0.05) as well as both ipsilateral and contralateral ABD EMGs by 35% and 48% ( P < 0.01 and P < 0.01, respectively). No cough depression was observed after microinjections of vehicle. There was no significant effect of microinjection of codeine in the cVRC (3.3 mM, 30–40 nl) on ABD activity induced by a microinjection of d,l-homocysteic acid (30 mM, 27–40 nl) in the same location. However, a cumulative dose of codeine (0.1 mg/kg, 330 nmol/kg) applied into the brain stem circulation through the vertebral artery reduced the ABD motor response to cVRC d,l-homocysteic acid microinjection (30 mM, 28–32 nl) by 47% ( P < 0.01). These results suggest that 1) codeine can act within the cVRC to suppress cough and 2) expiratory premotoneurons within the cVRC are relatively insensitive to this opioid.

Mormyromast electroreceptor organs and their afferent fibers in mormyrid fish. II. Intra-axonal recordings show initial stages of central processing

1990 ◽  
Vol 63 (2) ◽  
pp. 303-318 ◽  
Author(s):  
C. C. Bell
Keyword(s):  
Lateral Line ◽  
Electric Organ Discharge ◽  
Electric Organ ◽  
Direct Stimulation ◽  
Postsynaptic Potentials ◽  
Central Processing ◽  
Refractory Periods ◽  
Synaptic Potentials ◽  
Afferent Fibers ◽  
Stimulation Of

1. Physiologically and morphologically identified primary afferent fibers from mormyromast electroreceptor organs were recorded intracellularly. The fiber recordings were made from the nerve root of the posterior lateral line nerve, where the fibers enter the brain, and from the electrosensory lateral line lobe (ELL), near the central terminals of the fibers. 2. The intracellular recordings reveal a variety of potentials, synaptic and nonsynaptic, in addition to the large orthodromic action potentials from the periphery. The goal of the present study was to describe and interpret these various potentials in mormyromast afferent fibers as a first step in understanding the processing of electrosensory information in ELL. 3. Three types of synaptic potentials were recorded inside mormyromast afferent fibers: 1) electric organ corollary discharge (EOCD) excitatory postsynaptic potentials (EPSPs), driven by the motor command that elicits the electric organ discharge (EOD); 2) EPSPs evoked by electrosensory stimulation of electroreceptors in the skin near the electroreceptor from which the recorded fiber originates or by direct stimulation of an electrosensory nerve; and 3) inhibitory postsynaptic potentials (IPSPs) evoked by electrosensory stimulation of more distant electroreceptors. These synaptic potentials can be attributed to synaptic input to postsynaptic cells in ELL that is observed inside the afferent fibers because of electrical synapses between the fibers and the postsynaptic cells. 4. The peripherally evoked EPSPs could frequently be shown to be unitary. The unitary EPSPs were identical to the orthodromic spikes in originating from a single electroreceptor, in threshold, and in latency shift with increasing stimulus intensity. These similarities suggest that the unitary EPSPs are electrotonic EPSPs caused by impulses in other mormyromast afferent fibers that terminate on some of the same postsynaptic cells as the recorded fiber. The peripherally evoked IPSPs had a longer latency than the EPSPs or orthodromic spikes, requiring the presence of an inhibitory interneuron. 5. The peripherally evoked EPSPs, both unitary and nonunitary, show absolute refractory periods of 3-8 ms, followed by relative refractory periods of approximately 8 ms, when tested with two identical stimuli to a nerve. These refractory periods are interpreted as because of refractoriness in the fine preterminal branches of the axonal arbor. 6. A depolarizing afterpotential is commonly associated with the orthodromic spike and probably results from the successful propagation of the spike into the entire terminal arbor. The depolarizing afterpotential has a refractory period that is similar to that of the peripherally evoked EPSPs and that is also interpreted as refractoriness in the fine preterminal branches.(ABSTRACT TRUNCATED AT 400 WORDS)

Fastigial nucleus-mediated respiratory responses depend on the medullary gigantocellular nucleus

2001 ◽  
Vol 91 (4) ◽  
pp. 1713-1722 ◽  
Author(s):  
Fadi Xu ◽  
Tongrong Zhou ◽  
Tonya Gibson ◽  
Donald T. Frazier
Keyword(s):  
Electrical Stimulation ◽  
Ibotenic Acid ◽  
Major Effect ◽  
Fastigial Nucleus ◽  
Respiratory Response ◽  
The Right ◽  
Spontaneously Breathing ◽  
Respiratory Responses ◽  
Gigantocellular Nucleus ◽  
Stimulation Of

Electrical stimulation of the rostral fastigial nucleus (FNr) alters respiration via activation of local neurons. We hypothesized that this FNr-mediated respiratory response was dependent on the integrity of the nucleus gigantocellularis of the medulla (NGC). Electrical stimulation of the FNr in 15 anesthetized and tracheotomized spontaneously breathing rats significantly altered ventilation by 35.2 ± 11.0% ( P < 0.01) with the major effect being excitatory (78%). This respiratory response did not significantly differ from control after lesions of the NGC via bilateral microinjection of kainic or ibotenic acid (4.5 ± 1.9%; P > 0.05) but persisted in sham controls. Eight other rats, in which horseradish peroxidase (HRP) solution was previously microinjected into the left NGC, served as nonstimulation controls or were exposed to either 15-min repeated electrical stimulation of the right FNr or hypercapnia for 90 min. Histochemical and immunocytochemical data showed that the right FNr contained clustered HRP-labeled neurons, most of which were double labeled with c-Fos immunoreactivity in both electrically and CO2-stimulated rats. We conclude that the NGC receives monosynaptic FNr inputs and is required for fully expressing FNr-mediated respiratory responses.

Effect of neuropeptides released from sensory nerves on blood flow in the rat airway microcirculation

1992 ◽  
Vol 72 (4) ◽  
pp. 1563-1570 ◽  
Author(s):  
G. Piedimonte ◽  
J. I. Hoffman ◽  
W. K. Husseini ◽  
W. L. Hiser ◽  
J. A. Nadel
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Regional Blood Flow ◽  
Reference Sample ◽  
Left Ventricular ◽  
Sensory Nerves ◽  
Microvascular Blood Flow ◽  
Systemic Injection ◽  
Airway Mucosa ◽  
Stimulation Of

Stimulation of sensory nerves in the airway mucosa causes local release of the neuropeptides substance P and calcitonin gene-related peptide (CGRP). In this study we used a modification of the reference-sample microsphere technique to measure changes in regional blood flow and cardiac output distribution produced in the rat by substance P, CGRP, and capsaicin (a drug that releases endogenous neuropeptides from sensory nerves). Three sets of microspheres labeled with different radionuclides were injected into the left ventricle of anesthetized F344 rats before, immediately after, and 5 min after left ventricular injections of capsaicin, substance P, or CGRP. The reference blood sample was withdrawn from the abdominal aorta and was simultaneously replaced with 0.9% NaCl at 37 degrees C. We found that stimulation of sensory nerves with a low dose of capsaicin causes a large and selective increase in microvascular blood flow in the extrapulmonary airways. The effect of capsaicin is mimicked by systemic injection of substance P but not by CGRP, suggesting that substance P is the main agent of neurogenic vasodilation in rat airways.

In vivo study on medullary H(+)-sensitive neurons

1990 ◽  
Vol 69 (4) ◽  
pp. 1408-1412 ◽  
Author(s):  
N. Kogo ◽  
H. Arita
Keyword(s):  
Time Course ◽  
Direct Application ◽  
Ventrolateral Medulla ◽  
Similar Time ◽  
Central Chemoreceptors ◽  
Ph Dependent ◽  
Spontaneously Breathing ◽  
Medullary Neurons ◽  
Stimulation Of

Using the micro pressure ejection technique, we examined responses of medullary neurons with nonphasic discharges (164 units) to direct application of acidified mock cerebrospinal fluid (CSF, pH 6.85-7.05) in decerebrated spontaneously breathing cats. We found 16 H(+)-sensitive cells; they were excited promptly on application of approximately 500 pl of acidified mock CSF in the vicinity of the neuron under investigation, whereas they were unaffected by microejection of the control mock CSF (pH 7.25-7.60). Of the 16 H(+)-sensitive cells, 10 units were further found to be excited by transcapillary stimulation of the central chemoreceptors by using a method of intravertebral arterial injection of CO2-saturated saline. The discharges increased in a similar time course to that of ventilatory augmentation. Distributions of these 10 specific H(+)-sensitive cells were found in the vicinity of nucleus tractus solitarii as well as deep in the ventrolateral medulla. The present results suggest a possibility that pH-dependent central chemoreceptors, if any, would be located in two distinct medullary regions described in this study.

Cardiovascular-respiratory reflex interactions between carotid bodies and upper-airways receptors in the monkey

1978 ◽  
Vol 234 (3) ◽  
pp. H293-H299 ◽  
Author(s):  
M. B. Daly ◽  
P. I. Korner ◽  
J. E. Angell-James ◽  
J. R. Oliver
Keyword(s):  
Vascular Resistance ◽  
Pulmonary Ventilation ◽  
Superior Laryngeal Nerve ◽  
Macaque Monkey ◽  
Macaca Nemestrina ◽  
Upper Airways ◽  
Carotid Bodies ◽  
Spontaneously Breathing ◽  
Respiratory Stimulation ◽  
Stimulation Of

The carotid bodies were stimulated in the anesthetized pig-tailed macaque monkey (Macaca nemestrina) using i) brief injections of cyanide or CO2-equilibrated bicarbonate solution into a common carotid artery, and ii) longer perfusion with hypoxic hypercapnic blood in vascularly isolated chemoreceptor preparations. In spontaneously breathing animals, brief stimulations of the chemoreceptors consistently caused an increase in pulmonary ventilation, bradycardia, and an increase in femoral vascular resistance. When the same chemoreceptor stimulus was superimposed during the apneic period, reflexly evoked by stimulating either the central ends of the superior laryngeal nerves or the nasopharynx, the respiratory stimulation was absent or minimal, but the bradycardia and vasconstriction were greatly enhanced and exceeded the summed responses of separate stimulation of the chemoreceptors and one or the other of the upper-airways inputs. With sustained stimulation of the carotid bodies, hyperventilation, tachycardia, and femoral vasodilatation occurred due to overriding respiratory mechanisms. When superior laryngeal nerve stimulation was superimposed on this response, apnea occurred and tachycardia was reversed to bradycardia, and femoral vascular resistance increased above resting level. The interaction of autonomic responses resulting from chemoreceptor stimulation and from increases in the upper-airways inputs are qualitatively similar in the monkey and in subprimate species. Those involving specifically cardioinhibitory vagal responses are, in part at least, dependent on mechanisms related to the concomitant changes in respiration.

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