scholarly journals Hypersensitivity of Airway Reflexes Induced by Hydrogen Sulfide: Role of TRPA1 Receptors

2020 ◽  
Vol 21 (11) ◽  
pp. 3929
Author(s):  
Chi-Li Chung ◽  
You Shuei Lin ◽  
Nai-Ju Chan ◽  
Yueh-Yin Chen ◽  
Chun-Chun Hsu
Keyword(s):  
Hydrogen Sulfide ◽  
Enhancement Effect ◽  
Sodium Hydrosulfide ◽  
Cough Reflex ◽  
Functional Changes ◽  
Intracerebroventricular Infusion ◽  
Airway Reflex ◽  
Airway Hypersensitivity ◽  
Spontaneously Breathing

The activation of capsaicin-sensitive lung vagal (CSLV) afferents can elicit airway reflexes. Hypersensitivity of these afferents is known to contribute to the airway hypersensitivity during airway inflammation. Hydrogen sulfide (H2S) has been suggested as a potential therapeutic agent for airway hypersensitivity diseases, such as asthma, because of its relaxing effect on airway smooth muscle and anti-inflammatory effect. However, it is still unknown whether H2S affects airway reflexes. Our previous study demonstrated that exogenous application of H2S sensitized CSLV afferents and enhanced Ca2+ transients in CSLV neurons. The present study aimed to determine whether the H2S-induced sensitization leads to functional changes in airway reflexes and elevates the electrical excitability of the CSLV neurons. Our results showed that, first and foremost, in anesthetized, spontaneously breathing rats, the inhalation of aerosolized sodium hydrosulfide (NaHS, a donor of H2S; 5 mg/mL, 3 min) caused an enhancement in apneic response evoked by several stimulants of the CSLV afferents. This enhancement effect was found 5 min after NaHS inhalation and returned to control 30 min later. However, NaHS no longer enhanced the apneic response after perineural capsaicin treatment on both cervical vagi that blocked the conduction of CSLV fibers. Furthermore, the enhancing effect of NaHS on apneic response was totally abolished by pretreatment with intravenous HC-030031 (a TRPA1 antagonist; 8 mg/kg), whereas the potentiating effect was not affected by the pretreatment with the vehicle of HC-030031. We also found that intracerebroventricular infusion pretreated with HC-030031 failed to alter the potentiating effect of NaHS on the apneic response. Besides, the cough reflex elicited by capsaicin aerosol was enhanced by inhalation of NaHS in conscious guinea pigs. Nevertheless, this effect was entirely eliminated by pretreatment with HC-030031, not by its vehicle. Last but not least, voltage-clamp electrophysiological analysis of isolated rat CSLV neurons showed a similar pattern of potentiating effects of NaHS on capsaicin-induced inward current, and the involvement of TRPA1 receptors was also distinctly shown. In conclusion, these results suggest that H2S non-specifically enhances the airway reflex responses, at least in part, through action on the TRPA1 receptors expressed on the CSLV afferents. Therefore, H2S should be used with caution when applying for therapeutic purposes in airway hypersensitivity diseases.

scholarly journals Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced by 1,3-β-D-Glucan in Anesthetized Rats

2020 ◽  
Vol 21 (18) ◽  
pp. 6845
Author(s):  
You Shuei Lin ◽  
I-Hsuan Huang ◽  
Sheng-Hsuan Lan ◽  
Chia-Ling Chen ◽  
Yueh-Yin Chen ◽  
...  
Keyword(s):  
Pulmonary Inflammation ◽  
Intratracheal Instillation ◽  
Pathogenic Fungi ◽  
Vital Role ◽  
Irregular Pattern ◽  
Marked Enhancement ◽  
Ros Scavenger ◽  
Airway Hypersensitivity ◽  
Spontaneously Breathing

Airway exposure to 1,3-β-D-glucan (β-glucan), an essential component of the cell wall of several pathogenic fungi, causes various adverse responses, such as pulmonary inflammation and airway hypersensitivity. The former response has been intensively investigated; however, the mechanism underlying β-glucan-induced airway hypersensitivity is unknown. Capsaicin-sensitive lung vagal (CSLV) afferents are very chemosensitive and stimulated by various insults to the lungs. Activation of CSLV afferents triggers several airway reflexes, such as cough. Furthermore, the sensitization of these afferents is known to contribute to the airway hypersensitivity during pulmonary inflammation. This study was carried out to determine whether β-glucan induces airway hypersensitivity and the role of the CSLV neurons in this hypersensitivity. Our results showed that the intratracheal instillation of β-glucan caused not only a distinctly irregular pattern in baseline breathing, but also induced a marked enhancement in the pulmonary chemoreflex responses to capsaicin in anesthetized, spontaneously breathing rats. The potentiating effect of β-glucan was found 45 min later and persisted at 90 min. However, β-glucan no longer caused the irregular baseline breathing and the potentiating of pulmonary chemoreflex responses after treatment with perineural capsaicin treatment that blocked the conduction of CSLV fibers. Besides, the potentiating effect of β-glucan on pulmonary chemoreflex responses was significantly attenuated by N-acetyl-L-cysteine (a ROS scavenger), HC-030031 (a TRPA1 antagonist), and Laminarin (a Dectin-1 antagonist). A combination of Laminarin and HC-030031 further reduced the β-glucan-induced effect. Indeed, our fiber activity results showed that the baseline fiber activity and the sensitivity of CSLV afferents were markedly elevated by β-glucan instillation, with a similar timeframe in anesthetized, artificially ventilated rats. Moreover, this effect was reduced by treatment with HC-030031. In isolated rat CSLV neurons, the β-glucan perfusion caused a similar pattern of potentiating effects on capsaicin-induced Ca2+ transients, and β-glucan-induced sensitization was abolished by Laminarin pretreatment. Furthermore, the immunofluorescence results showed that there was a co-localization of TRPV1 and Dectin-1 expression in the DiI-labeled lung vagal neurons. These results suggest that CSLV afferents play a vital role in the airway hypersensitivity elicited by airway exposure to β-glucan. The TRPA1 and Dectin-1 receptors appear to be primarily responsible for generating β-glucan-induced airway hypersensitivity.

scholarly journals Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of BK channels

2010 ◽  
Vol 299 (5) ◽  
pp. H1554-H1567 ◽  
Author(s):  
Mozow Y. Zuidema ◽  
Yan Yang ◽  
Meifang Wang ◽  
Theodore Kalogeris ◽  
Yajun Liu ◽  
...  
Keyword(s):  
Small Intestine ◽  
Hydrogen Sulfide ◽  
Ischemia Reperfusion ◽  
Bk Channels ◽  
Bk Channel ◽  
Confocal Imaging ◽  
Sodium Hydrosulfide ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

The objectives of this study were to determine the role of calcium-activated, small (SK), intermediate (IK), and large (BK) conductance potassium channels in initiating the development of an anti-inflammatory phenotype elicited by preconditioning with an exogenous hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS). Intravital microscopy was used to visualize rolling and firmly adherent leukocytes in vessels of the small intestine of mice preconditioned with NaHS (in the absence and presence of SK, IK, and BK channel inhibitors, apamin, TRAM-34, and paxilline, respectively) or SK/IK (NS-309) or BK channel activators (NS-1619) 24 h before ischemia-reperfusion (I/R). I/R induced marked increases in leukocyte rolling and adhesion, effects that were largely abolished by preconditioning with NaHS, NS-309, or NS-1619. The postischemic anti-inflammatory effects of NaHS-induced preconditioning were mitigated by BKB channel inhibitor treatment coincident with NaHS, but not by apamin or TRAM-34, 24 h before I/R. Confocal imaging and immunohistochemistry were used to demonstrate the presence of BKα subunit staining in both endothelial and vascular smooth muscle cells of isolated, pressurized mesenteric venules. Using patch-clamp techniques, we found that BK channels in cultured endothelial cells were activated after exposure to NaHS. Bath application of the same concentration of NaHS used in preconditioning protocols led to a rapid increase in a whole cell K+ current; specifically, the component of K+ current blocked by the selective BK channel antagonist iberiotoxin. The activation of BK current by NaHS could also be demonstrated in single channel recording mode where it was independent of a change in intracellular Ca+ concentration. Our data are consistent with the concept that H2S induces the development of an anti-adhesive state in I/R in part mediated by a BK channel-dependent mechanism.

scholarly journals Hydrogen sulfide alleviates chlorobenzene toxicity in soybean seedlings

2016 ◽  
Vol 46 (10) ◽  
pp. 1743-1749 ◽  
Author(s):  
Jin Feng Chen ◽  
Chan Jiao
Keyword(s):  
Hydrogen Sulfide ◽  
Plant Stress ◽  
Root Growth Inhibition ◽  
Oxygen Species ◽  
Cell Toxicity ◽  
Sodium Hydrosulfide ◽  
Soybean Seedlings ◽  
Cysteine Desulfhydrase ◽  
Pre Treatment

ABSTRACT: As a gas signaling molecule, endogenous hydrogen sulfide (H2S) plays a crucial role in the plant stress response. However, the role of H2S in the response to organic pollutants specifically has not been studied. Here, the effects of H2S addition on soybean (Glycine max) seedlings tolerance of 1,4-dichlorobenzene (1,4-DCB) were investigated. Under 1,4-DCB stress, the growth of soybean seedlings roots and stems was inhibited, while L-/D-cysteine desulfhydrase (LCD/DCD) activity was induced and endogenous H2S increased. When applied jointly with sodium hydrosulfide (NaHS), a H2S donor, root growth inhibition was effectively alleviated. Pre-treatment of seedlings with 0.4mmol L-1 NaHS reduced the malondialdehyde (MDA) and reactived oxygen species (ROS) content, mitigating root cell toxicity significantly. Further experiments confirmed that NaHS enhanced soybean seedlings peroxidase (POD) and superoxide dismutase (SOD) enzyme activities. In contrast, these effects were reversed by hypotaurine (HT), a H2S scavenger. Therefore, H2S alleviated 1,4-DCB toxicity in soybean seedlings by regulating antioxidant enzyme activity to reduce cell oxidative damage.

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.

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 The Effect of a Fast-Releasing Hydrogen Sulfide Donor on Vascularization of Subcutaneous Scaffolds in Immunocompetent and Immunocompromised Mice

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 722 ◽  
Author(s):  
Alexandra M. Smink ◽  
Avid Najdahmadi ◽  
Michael Alexander ◽  
Shiri Li ◽  
Samuel Rodriquez ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Immune System ◽  
Nude Mice ◽  
Polymer Scaffolds ◽  
Sodium Hydrosulfide ◽  
Glucose Levels ◽  
Gene And Protein Expression ◽  
Immunocompromised Mice

Islet transplantation into subcutaneous polymer scaffolds has shown to successfully induce normoglycemia in type 1 diabetes models. Vascularization of these scaffolds is imperative for optimal control of glucose levels. We studied the effect of the vascular stimulator hydrogen sulfide (H2S) on the degree of vascularization of a scaffold and the role of the immune system in this process. Scaffolds were subcutaneously implanted in immunocompetent C57BL/6 and immunocompromised nude mice. Mice received twice-daily intraperitoneal injections of the fast-releasing H2S donor sodium hydrosulfide (NaHS, 25 or 50 μmol/kg) or saline for 28 days. After 63 days the vascular network was analyzed by histology and gene expression. Here we showed that the vascularization of a subcutaneous scaffold in nude mice was significantly impaired by H2S treatment. Both the CD31 gene and protein expression were reduced in these scaffolds compared to the saline-treated controls. In C57BL/6 mice, the opposite was found, the vascularization of the scaffold was significantly increased by H2S. The mRNA expression of the angiogenesis marker CD105 was significantly increased compared to the controls as well as the number of CD31 positive blood vessels. In conclusion, the immune system plays an important role in the H2S mediated effect on vascularization of subcutaneous scaffolds.

scholarly journals Hydrogen Sulfide-Mediated Activation of O-Acetylserine (Thiol) Lyase and l/d-Cysteine Desulfhydrase Enhance Dehydration Tolerance in Eruca sativa Mill

2018 ◽  
Vol 19 (12) ◽  
pp. 3981 ◽  
Author(s):  
M. Khan ◽  
Fahad AlZuaibr ◽  
Asma Al-Huqail ◽  
Manzer Siddiqui ◽  
Hayssam M. Ali ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Hydrogen Sulfide ◽  
Membrane Permeability ◽  
Water Status ◽  
Carbonic Anhydrase Activity ◽  
Dehydration Stress ◽  
Eruca Sativa ◽  
Sodium Hydrosulfide ◽  
Cysteine Desulfhydrase

Hydrogen sulfide (H2S) has emerged as an important signaling molecule and plays a significant role during different environmental stresses in plants. The present work was carried out to explore the potential role of H2S in reversal of dehydration stress-inhibited O-acetylserine (thiol) lyase (OAS-TL), l-cysteine desulfhydrase (LCD), and d-cysteine desulfhydrase (DCD) response in arugula (Eruca sativa Mill.) plants. Dehydration-stressed plants exhibited reduced water status and increased levels of hydrogen peroxide (H2O2) and superoxide (O2•−) content that increased membrane permeability and lipid peroxidation, and caused a reduction in chlorophyll content. However, H2S donor sodium hydrosulfide (NaHS), at the rate of 2 mM, substantially reduced oxidative stress (lower H2O2 and O2•−) by upregulating activities of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase) and increasing accumulation of osmolytes viz. proline and glycine betaine (GB). All these, together, resulted in reduced membrane permeability, lipid peroxidation, water loss, and improved hydration level of plants. The beneficial role of H2S in the tolerance of plants to dehydration stress was traced with H2S-mediated activation of carbonic anhydrase activity and enzyme involved in the biosynthesis of cysteine (Cys), such as OAS-TL. H2S-treated plants showed maximum Cys content. The exogenous application of H2S also induced the activity of LCD and DCD enzymes that assisted the plants to synthesize more H2S from accumulated Cys. Therefore, an adequate concentration of H2S was maintained, that improved the efficiency of plants to mitigate dehydration stress-induced alterations. The central role of H2S in the reversal of dehydration stress-induced damage was evident with the use of the H2S scavenger, hypotaurine.

Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats

2007 ◽  
Vol 102 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Yi Zhun Zhu ◽  
Zhong Jing Wang ◽  
Peiying Ho ◽  
Yoke Yun Loke ◽  
Yi Chun Zhu ◽  
...  
Keyword(s):  
Cell Death ◽  
Hydrogen Sulfide ◽  
Rat Model ◽  
Protein Localization ◽  
Sodium Hydrosulfide ◽  
Infarct Area ◽  
Novel Approach ◽  
First Time

The role of hydrogen sulfide (H2S) in myocardial infarction (MI) has not been previously studied. We therefore investigated the effect of H2S in a rat model of MI in vivo. Animals were randomly divided into three groups ( n = 80) and received either vehicle, 14 μmol/kg of sodium hydrosulfide (NaHS), or 50 mg/kg propargylglycine (PAG) everyday for 1 wk before surgery, and the treatment was continued for a further 2 days after MI when the animals were killed. The mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS-treated ( P < 0.05 vs. vehicle) groups. Infarct size was 52.9 ± 3.5% in vehicle-treated, 62.9 ± 7.6% in PAG-treated, and 43.4 ± 2.8% in NaHS-treated ( P < 0.05 vs. vehicle) groups. Plasma H2S concentration was significantly increased after MI (59.2 ± 7.16 μM) compared with the baseline concentration (i.e., 38.2 ± 2.07 μM before MI; P < 0.05). Elevated plasma H2S after MI was abolished by treatment of animals with PAG (39.2 ± 5.02 μM). We further showed for the first time cystathionine-gamma-lyase protein localization in the myocardium of the infarct area by using immunohistochemical staining. In the hypoxic vascular smooth muscle cells, we found that cell death was increased under the stimuli of hypoxia but that the increased cell death was attenuated by the pretreatment of NaHS (71 ± 1.2% cell viability in hypoxic vehicle vs. 95 ± 2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H2S was cardioprotective in the rat model of MI. PAG reduced endogenous H2S production after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H2S might provide a novel approach to the treatment of MI.

Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse

2006 ◽  
Vol 290 (6) ◽  
pp. L1193-L1201 ◽  
Author(s):  
Huili Zhang ◽  
Liang Zhi ◽  
Philip K. Moore ◽  
Madhav Bhatia
Keyword(s):  
Hydrogen Sulfide ◽  
Systemic Inflammation ◽  
Mammalian Cells ◽  
Cecal Ligation ◽  
Organ Injury ◽  
Sham Operation ◽  
Myeloperoxidase Activity ◽  
Cecal Ligation And Puncture ◽  
Sodium Hydrosulfide

Endogenous hydrogen sulfide (H2S) is naturally synthesized in various types of mammalian cells from l-cysteine in a reaction catalyzed by two enzymes, cystathionine-γ-lyase (CSE) and/or cystathionine-β-synthase. The latest studies have implied that H2S functions as a vasodilator and neurotransmitter. However, so far there is little information about the role played by H2S in systemic inflammation such as sepsis. Thus the aim of this study was to investigate the potential role of endogenous H2S in cecal ligation and puncture (CLP)-induced sepsis. Male Swiss mice were subjected to CLP-induced sepsis and treated with saline (ip), dl-propargylglycine (PAG, 50 mg/kg ip), a CSE inhibitor, or sodium hydrosulfide (NaHS; 10 mg/kg ip). PAG was administered either 1 h before or 1 h after the induction of sepsis, whereas NaHS was given at the same time of CLP. CLP-induced sepsis significantly increased the plasma H2S level and the liver H2S synthesis 8 h after CLP compared with sham operation. Induction of sepsis also resulted in a significant upregulation of CSE mRNA in liver. On the other hand, prophylactic as well as therapeutic administration of PAG significantly reduced sepsis-associated systemic inflammation, as evidenced by myeloperoxidase activity and histological changes in lung and liver, and attenuated the mortality of CLP-induced sepsis. Injection of NaHS significantly aggravated sepsis-associated systemic inflammation. Therefore, the effect of inhibition of H2S formation and administration of NaHS suggests that H2S plays a proinflammatory role in regulating the severity of sepsis and associated organ injury.

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