Immediate sensory nerve-mediated respiratory responses  to irritants in healthy and allergic airway-diseased mice

Morris, John B.; Symanowicz, Peter T.; Olsen, Joshua E.; Thrall, Roger S.; Cloutier, Michelle M.; Hubbard, Andrea K.

doi:10.1152/japplphysiol.00572.2002

Cited by 56 publications

(46 citation statements)

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“…We confirmed this by challenging the mice with acetic acid aerosol, a known respiratory irritant whose effects are mediated by chemosensory C-fibers (54). When we exposed Trpa1 -/-mice to acetic acid aerosol, we observed a decline in respiratory frequency and an increase in EEP (Supplemental Figure 2, A and B) similar to data reported in previous studies (54 Our initial experiments showed that TRPA1 is the primary target through which the oxidant chlorine excites sensory neurons and activates respiratory depression. In order to determine whether TRPA1 is also a target for other oxidant stimuli, including reactive oxygen species, we examined the effects of H 2 O 2 on sensory neuronal activity.…”

Section: Figuresupporting

confidence: 86%

“…Indeed, a recent study showed that H 2 O 2 -induced changes in respiratory frequency can be inhibited, at least in part, by a purinergic receptor antagonist (23). Involvement of additional neuronal pathways may explain why we observed residual respira- (4,54,81). These exaggerated responses may be the result of sensitization of TRPA1 downstream of neuronal phospholipase C-coupled receptor systems activated during inflammation, including the receptors for bradykinin, histamine, proteases, and other inflammatory stimuli (36,37,42,82,83).…”

Section: Discussionmentioning

confidence: 75%

“…In addition, significant increases in end expiratory pause (EEP; the period of end expiratory flow) were observed (14). Respiratory rate depression and increased EEP are characteristic for nasal irritant responses, as shown by studies examining the effects of chlorine and numerous other sensory irritants (54)(55)(56)(57)(58)(59). These changes in respiratory rate and waveform appeared to be induced by upper airway reflexes following activation of nasal trigeminal sensory nerve endings by OCl - (14).…”

Section: Figurementioning

confidence: 96%

“…We compared the respiratory responses of Trpa1 +/+ and Trpa1 -/-mice to NaOCl aerosol exposure by barometric plethysmography, a method used extensively in the study of sensory irritation by chlorine and other irritants (14,53,54). Earlier studies using this method showed that mice respond to low-level chlorine or NaOCl aerosol exposure with a rapid decline in respiratory frequency (14).…”

Section: Figurementioning

confidence: 99%

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TRPA1 is a major oxidant sensor in murine airway sensory neurons

Bessac¹,

Sivula²,

Hehn³

et al. 2008

J. Clin. Invest.

404

394

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Sensory neurons in the airways are finely tuned to respond to reactive chemicals threatening airway function and integrity. Nasal trigeminal nerve endings are particularly sensitive to oxidants formed in polluted air and during oxidative stress as well as to chlorine, which is frequently released in industrial and domestic accidents. Oxidant activation of airway neurons induces respiratory depression, nasal obstruction, sneezing, cough, and pain. While normally protective, chemosensory airway reflexes can provoke severe complications in patients affected by inflammatory airway conditions like rhinitis and asthma. Here, we showed that both hypochlorite, the oxidizing mediator of chlorine, and hydrogen peroxide, a reactive oxygen species, activated Ca 2+ influx and membrane currents in an oxidant-sensitive subpopulation of chemosensory neurons. These responses were absent in neurons from mice lacking TRPA1, an ion channel of the transient receptor potential (TRP) gene family. TRPA1 channels were strongly activated by hypochlorite and hydrogen peroxide in primary sensory neurons and heterologous cells. In tests of respiratory function, Trpa1 -/-mice displayed profound deficiencies in hypochlorite-and hydrogen peroxide-induced respiratory depression as well as decreased oxidant-induced pain behavior. Our results indicate that TRPA1 is an oxidant sensor in sensory neurons, initiating neuronal excitation and subsequent physiological responses in vitro and in vivo.

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Section: Figuresupporting

confidence: 86%

Section: Discussionmentioning

confidence: 75%

Section: Figurementioning

confidence: 96%

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

TRPA1 is a major oxidant sensor in murine airway sensory neurons

Bessac¹,

Sivula²,

Hehn³

et al. 2008

J. Clin. Invest.

404

394

View full text Add to dashboard Cite

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“…When OC was sprayed into the face of the sensitized and normal guinea pigs for 1 or 4 s, bronchoconstriction was observed, and the sensitized animals were more sensitive [19]. Several in vivo studies on mice showed RD 50 (the concentration of a chemical required to produce a 50% decrease in respiratory rate for sensory irritants) levels between 0.2 mg/m 3 to 10.4 mg/m 3 [20,21].…”

Section: Experimental Studies On Oc Cs and Mechanisms Of Actionmentioning

confidence: 99%

Effects of Tear Gases on the Pulmonary System

Arbak¹

2013

Tur Toraks Der

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The acute effects of tear gases such as oleoresincapsicum and 2-chlorobenzylidene malononitrile are well known. Tear gases cause incapacitating inflammatory response in various tissues and organs including the lungs, eyes, nose, throat, skin and others. The final results on the pulmonary system are toxic pneumonitis, asthma aggravation, bronchitis, and rhinitis. Long term effects are irritant induced asthma and chronic obstructive pulmonary disorders. The best way to reduce the hazardous effects of these gases is not to use them at all. Key words: Tear gases, respiratory effects, lung diseasesOleoresincapsicum ve 2-chlorobenzylidene malononitrile gibi göz yaşartan gazların akut etkileri iyi bilinmektedir. Göz yaşartan gazlar akciğerler, gözler, burun, boğaz, cildi içeren çeşitli doku ve organlarda güçsüz bırakan yangısal yanıta yol açmaktadırlar. Solunum sistemi üstündeki son sonuçlar toksik pnömonitis, astım alevlenmesi, bronşit ve rinittir. Uzun dönemli etkileri ise irritanla indüklenen astım, kronik obstrüktif solunumsal hastalıklardır. Bu gazların zararlı etkilerini azaltmanın en iyi yolu onları hiç kullanmamaktır. AnAhtAr sözcüKler: Göz yaşartan gazlar, solunumsal etkiler, akciğer hastalıkları IntrodUctIonThe Turkish Police Department reported that they mostly used Oleoresincapsicum (OC) and 2-chlorobenzylidene malononitrile (CS) as tear gases for controlling protest actions [1]. OC is an organic resin derived from the pepper plant and its toxicological effect is mainly dependent on the amount of capsiacinoids in it. The capsaicinoid content determines the "hotness" of the OC product, measured in Scoville units. OC for nonlethal weapon formulas can differ in potency from 16000 Scoville Heat Units (S.H.U) to1.5 million units, with a 5-10% solution generally recommended as an effective dose [2]. When used, OC causes incapacitating inflammatory response in various tissues and organs including the lungs, eyes, nose, throat, skin and others [3]. OC leads to wheezing, dry cough, shortness of breath, gasping, difficulty in breathing or speaking due to laryngospasm and rarely cyanosis, apnoea, and respiratory arrest in the respiratory system [4].Chlorobenzylidenemalononitrile is a white crystalline substance that is usually mixed with the other compounds in a grenade or canister for use. The preferable form for scattering populations is intended to be a smoke or fog of suspended particles. Being an extremely severe skin and mucous membrane irritant and lacrimator, even at minute doses, CS is found to be effective for controlling crowds [5]. Respiratory symptoms due to CS are nasal irritation, rhinorrhea, coughing and shortness of breath [6]. The effects of CS usually start after 20 to 60 seconds of exposure and resolve within 30 minutes [7]. Animal studies showed that the respiratory concentration of CS 25000 to 150000 mg/m 3 per minute would be lethal for 50% of healthy adults. When used outside, a CS grenade produces a cloud 6-9 meters in diameter, the highest CS concentration of 2000 to 5000 mg/m 3 is detected a...

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Simultaneous determination of free and total glycerol in biodiesel by capillary electrophoresis using multiple short‐end injection

et al. 2013

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A rapid method for the simultaneous determination of free glycerol (FG) and total glycerol (TG) in biodiesel by CE using a short-end multiple injection (SE/MI) configuration system is described. The sample preparation for FG involves the extraction of glycerol with water and for TG a saponification reaction is carried out followed by extraction as in the case of FG. The glycerol extracted in both cases is submitted to periodate oxidation and the iodate ions formed are measured on a CE-SE/MI system. The relevance of this study lies in the fact that no analytical procedure has been previously reported for the determination of TG (or of FG and TG simultaneously) by CE. The optimum conditions for the saponification/extraction process were 1.25% KOH and 25°C, with a time of only 5 min, and biodiesel mass in the range of 50.0-200.0 mg can be used. Multiple injections were performed hydrodynamically with negative pressure as follows: 50 mbar/3s (FG sample); 50 mbar/6s (electrolyte spacer); 50 mbar/3s (TG sample). The linear range obtained was 1.55-46.5 mg/L with R(2) > 0.99. The LOD and LOQ were 0.16 mg/L and 0.47 mg/L, respectively for TG. The method provides acceptable throughput for application in quality control and monitoring biodiesel synthesis process. In addition, it offers simple sample preparation (saponification process), it can be applied to a variety biodiesel samples (soybean, castor, and waste cooking oils) and it can be used for the determination of two key parameters related to the biodiesel quality with a fast separation (less than 30 s) using an optimized CE-SE/MI system.

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Immediate sensory nerve-mediated respiratory responses to irritants in healthy and allergic airway-diseased mice

Abstract: . Immediate sensory nerve-mediated respiratory responses to irritants in healthy and allergic airway-diseased mice.

Cited by 56 publications

References 45 publications

TRPA1 is a major oxidant sensor in murine airway sensory neurons

TRPA1 is a major oxidant sensor in murine airway sensory neurons

Effects of Tear Gases on the Pulmonary System

Simultaneous determination of free and total glycerol in biodiesel by capillary electrophoresis using multiple short‐end injection

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