Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C‐fibres
Key points Brief inhalation of SO2 of concentration >500 p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C‐fibres in anaesthetized rats. This stimulatory effect was drastically diminished by a pretreatment with NaHCO3 that raised the baseline arterial pH, suggesting a p...
Gespeichert in:
| Veröffentlicht in: | The Journal of physiology 2020-03, Vol.598 (5), p.1093-1108 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1108 |
|---|---|
| container_issue | 5 |
| container_start_page | 1093 |
| container_title | The Journal of physiology |
| container_volume | 598 |
| creator | Lin, An‐Hsuan Hsu, Chun‐Chun Lin, You Shuei Lin, Ruei‐Lung Lee, Lu‐Yuan |
| description | Key points
Brief inhalation of SO2 of concentration >500 p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C‐fibres in anaesthetized rats.
This stimulatory effect was drastically diminished by a pretreatment with NaHCO3 that raised the baseline arterial pH, suggesting a possible involvement of acidification of airway fluid and/or tissue generated by inhaled SO2.
The stimulation was completely abolished by pretreatment with antagonists of both acid‐sensing ion channels and transient receptor potential vanilloid type‐1 receptors, indicating that this effect was caused by acid activation of these cation channels expressed in airway sensory nerves.
This conclusion was further supported by the results obtained from studies in isolated rat vagal bronchopulmonary sensory neurones and also in the cough response to SO2 inhalation challenge in awake mice.
These results provide new insight into the underlying mechanism of harmful irritant effects in the respiratory tract caused by accidental exposure to a high concentration of SO2.
Inhalation of sulfur dioxide (SO2) triggers coughs and reflex bronchoconstriction, and stimulation of vagal bronchopulmonary C‐fibres is primarily responsible. However, the mechanism underlying this stimulatory effect is not yet fully understood. In this study, we tested the hypothesis that the C‐fibre stimulation was caused by SO2‐induced local tissue acidosis in the lung and airways. Single‐unit activities of bronchopulmonary C‐fibres in response to inhalation challenges of SO2 (500–1500 p.p.m., 10 breaths) were measured in anaesthetized rats. Inhalation of SO2 reproducibly induced a pronounced and sustained stimulation (lasting for 15–60 s) of pulmonary C‐fibres in a concentration‐dependent manner. This stimulatory effect was significantly attenuated by an increase in arterial pH generated by infusion of sodium bicarbonate (NaHCO3), and completely abrogated by a combined pretreatment with amiloride (an antagonist of acid‐sensing ion channels, ASICs) and AMG8910 (a selective antagonist of the transient receptor potential vanilloid type‐1 receptor, TRPV1). Furthermore, in isolated rat vagal pulmonary sensory neurones, perfusion of an aqueous solution of SO2 evoked a transient increase in the intracellular Ca2+ concentration; this response was also markedly diminished by a pretreatment with amiloride and AMG8910. In addition, inhalation of SO2 consistently evoked coughs in awake mice; responses were significantly s |
| doi_str_mv | 10.1113/JP279152 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7050412</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2365872219</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4396-8472da638de85ff10b1ed747ed041da9df38a461146e772d15297bdba92420bb3</originalsourceid><addsrcrecordid>eNp1kc9u1DAQxi0EosuCxBMgS1y4pPhPEscXJLTiT6tW9FDOlhOPNy6OvdhJYW88As_Ik-Bq2woOPc1hfvPNN_Mh9JKSY0opf3t6wYSkDXuEVrRuZSWE5I_RihDGKi4aeoSe5XxFCOVEyqfoiNNOUir5Cn07h2HUweUp4yUYSH7vwhbPI-A8u2nxeo5pj8FaGGYcLXZh1B4Mzou3S8LGxZ_OAI4BX-ut9rhPMQxj3C1-ikGX0c2fX7-t6xPk5-iJ1T7Di9u6Rl8_frjcfK7Ovnw62bw_q4aay7bqasGMbnlnoGuspaSnYEQtwJCaGi2N5Z2uW1ouBVHQcrcUvem1ZDUjfc_X6N1Bd7f0E5gBwpy0V7vkpmJIRe3U_53gRrWN10qQpqxgReD1rUCK3xfIs7qKSwrFs2K8bTrBWHneGr05UEOKOSew9xsoUTexqLtYCvrqX0f34F0OBTg-AD-ch_2DQury9IJy2bT8L-XgmQc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2365872219</pqid></control><display><type>article</type><title>Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C‐fibres</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Lin, An‐Hsuan ; Hsu, Chun‐Chun ; Lin, You Shuei ; Lin, Ruei‐Lung ; Lee, Lu‐Yuan</creator><creatorcontrib>Lin, An‐Hsuan ; Hsu, Chun‐Chun ; Lin, You Shuei ; Lin, Ruei‐Lung ; Lee, Lu‐Yuan</creatorcontrib><description>Key points
Brief inhalation of SO2 of concentration >500 p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C‐fibres in anaesthetized rats.
This stimulatory effect was drastically diminished by a pretreatment with NaHCO3 that raised the baseline arterial pH, suggesting a possible involvement of acidification of airway fluid and/or tissue generated by inhaled SO2.
The stimulation was completely abolished by pretreatment with antagonists of both acid‐sensing ion channels and transient receptor potential vanilloid type‐1 receptors, indicating that this effect was caused by acid activation of these cation channels expressed in airway sensory nerves.
This conclusion was further supported by the results obtained from studies in isolated rat vagal bronchopulmonary sensory neurones and also in the cough response to SO2 inhalation challenge in awake mice.
These results provide new insight into the underlying mechanism of harmful irritant effects in the respiratory tract caused by accidental exposure to a high concentration of SO2.
Inhalation of sulfur dioxide (SO2) triggers coughs and reflex bronchoconstriction, and stimulation of vagal bronchopulmonary C‐fibres is primarily responsible. However, the mechanism underlying this stimulatory effect is not yet fully understood. In this study, we tested the hypothesis that the C‐fibre stimulation was caused by SO2‐induced local tissue acidosis in the lung and airways. Single‐unit activities of bronchopulmonary C‐fibres in response to inhalation challenges of SO2 (500–1500 p.p.m., 10 breaths) were measured in anaesthetized rats. Inhalation of SO2 reproducibly induced a pronounced and sustained stimulation (lasting for 15–60 s) of pulmonary C‐fibres in a concentration‐dependent manner. This stimulatory effect was significantly attenuated by an increase in arterial pH generated by infusion of sodium bicarbonate (NaHCO3), and completely abrogated by a combined pretreatment with amiloride (an antagonist of acid‐sensing ion channels, ASICs) and AMG8910 (a selective antagonist of the transient receptor potential vanilloid type‐1 receptor, TRPV1). Furthermore, in isolated rat vagal pulmonary sensory neurones, perfusion of an aqueous solution of SO2 evoked a transient increase in the intracellular Ca2+ concentration; this response was also markedly diminished by a pretreatment with amiloride and AMG8910. In addition, inhalation of SO2 consistently evoked coughs in awake mice; responses were significantly smaller in TRPV1−/− mice than in wild‐type mice, and almost completely abolished after a pretreatment with amiloride in TRPV1−/− mice. These results suggested that the stimulatory effect of inhaled SO2 on bronchopulmonary C‐fibres was generated by acidification of fluid and/or tissue in the lung and airways, which activated both ASICs and TRPV1 expressed in these sensory nerves.
Key points
Brief inhalation of SO2 of concentration >500 p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C‐fibres in anaesthetized rats.
This stimulatory effect was drastically diminished by a pretreatment with NaHCO3 that raised the baseline arterial pH, suggesting a possible involvement of acidification of airway fluid and/or tissue generated by inhaled SO2.
The stimulation was completely abolished by pretreatment with antagonists of both acid‐sensing ion channels and transient receptor potential vanilloid type‐1 receptors, indicating that this effect was caused by acid activation of these cation channels expressed in airway sensory nerves.
This conclusion was further supported by the results obtained from studies in isolated rat vagal bronchopulmonary sensory neurones and also in the cough response to SO2 inhalation challenge in awake mice.
These results provide new insight into the underlying mechanism of harmful irritant effects in the respiratory tract caused by accidental exposure to a high concentration of SO2.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/JP279152</identifier><identifier>PMID: 31891193</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Acidification ; Acidosis ; Amiloride ; Animals ; ASIC ; Bronchi ; Bronchoconstriction ; Calcium (intracellular) ; Capsaicin receptors ; chemical irritant ; cough ; Fibers ; Inhalation ; Ion channels ; Lung ; lung injury ; Mice ; Nerve Fibers, Unmyelinated ; Perfusion ; Rats ; Sensory neurons ; Sodium bicarbonate ; Sulfur ; Sulfur dioxide ; Sulfur Dioxide - toxicity ; Transient receptor potential proteins ; TRPV Cation Channels ; TRPV1 ; Vagus Nerve</subject><ispartof>The Journal of physiology, 2020-03, Vol.598 (5), p.1093-1108</ispartof><rights>2019 The Authors. The Journal of Physiology © 2019 The Physiological Society</rights><rights>2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.</rights><rights>Journal compilation © 2020 The Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4396-8472da638de85ff10b1ed747ed041da9df38a461146e772d15297bdba92420bb3</citedby><cites>FETCH-LOGICAL-c4396-8472da638de85ff10b1ed747ed041da9df38a461146e772d15297bdba92420bb3</cites><orcidid>0000-0001-8545-2222 ; 0000-0001-8306-2845</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050412/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050412/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31891193$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, An‐Hsuan</creatorcontrib><creatorcontrib>Hsu, Chun‐Chun</creatorcontrib><creatorcontrib>Lin, You Shuei</creatorcontrib><creatorcontrib>Lin, Ruei‐Lung</creatorcontrib><creatorcontrib>Lee, Lu‐Yuan</creatorcontrib><title>Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C‐fibres</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>Key points
Brief inhalation of SO2 of concentration >500 p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C‐fibres in anaesthetized rats.
This stimulatory effect was drastically diminished by a pretreatment with NaHCO3 that raised the baseline arterial pH, suggesting a possible involvement of acidification of airway fluid and/or tissue generated by inhaled SO2.
The stimulation was completely abolished by pretreatment with antagonists of both acid‐sensing ion channels and transient receptor potential vanilloid type‐1 receptors, indicating that this effect was caused by acid activation of these cation channels expressed in airway sensory nerves.
This conclusion was further supported by the results obtained from studies in isolated rat vagal bronchopulmonary sensory neurones and also in the cough response to SO2 inhalation challenge in awake mice.
These results provide new insight into the underlying mechanism of harmful irritant effects in the respiratory tract caused by accidental exposure to a high concentration of SO2.
Inhalation of sulfur dioxide (SO2) triggers coughs and reflex bronchoconstriction, and stimulation of vagal bronchopulmonary C‐fibres is primarily responsible. However, the mechanism underlying this stimulatory effect is not yet fully understood. In this study, we tested the hypothesis that the C‐fibre stimulation was caused by SO2‐induced local tissue acidosis in the lung and airways. Single‐unit activities of bronchopulmonary C‐fibres in response to inhalation challenges of SO2 (500–1500 p.p.m., 10 breaths) were measured in anaesthetized rats. Inhalation of SO2 reproducibly induced a pronounced and sustained stimulation (lasting for 15–60 s) of pulmonary C‐fibres in a concentration‐dependent manner. This stimulatory effect was significantly attenuated by an increase in arterial pH generated by infusion of sodium bicarbonate (NaHCO3), and completely abrogated by a combined pretreatment with amiloride (an antagonist of acid‐sensing ion channels, ASICs) and AMG8910 (a selective antagonist of the transient receptor potential vanilloid type‐1 receptor, TRPV1). Furthermore, in isolated rat vagal pulmonary sensory neurones, perfusion of an aqueous solution of SO2 evoked a transient increase in the intracellular Ca2+ concentration; this response was also markedly diminished by a pretreatment with amiloride and AMG8910. In addition, inhalation of SO2 consistently evoked coughs in awake mice; responses were significantly smaller in TRPV1−/− mice than in wild‐type mice, and almost completely abolished after a pretreatment with amiloride in TRPV1−/− mice. These results suggested that the stimulatory effect of inhaled SO2 on bronchopulmonary C‐fibres was generated by acidification of fluid and/or tissue in the lung and airways, which activated both ASICs and TRPV1 expressed in these sensory nerves.
Key points
Brief inhalation of SO2 of concentration >500 p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C‐fibres in anaesthetized rats.
This stimulatory effect was drastically diminished by a pretreatment with NaHCO3 that raised the baseline arterial pH, suggesting a possible involvement of acidification of airway fluid and/or tissue generated by inhaled SO2.
The stimulation was completely abolished by pretreatment with antagonists of both acid‐sensing ion channels and transient receptor potential vanilloid type‐1 receptors, indicating that this effect was caused by acid activation of these cation channels expressed in airway sensory nerves.
This conclusion was further supported by the results obtained from studies in isolated rat vagal bronchopulmonary sensory neurones and also in the cough response to SO2 inhalation challenge in awake mice.
These results provide new insight into the underlying mechanism of harmful irritant effects in the respiratory tract caused by accidental exposure to a high concentration of SO2.</description><subject>Acidification</subject><subject>Acidosis</subject><subject>Amiloride</subject><subject>Animals</subject><subject>ASIC</subject><subject>Bronchi</subject><subject>Bronchoconstriction</subject><subject>Calcium (intracellular)</subject><subject>Capsaicin receptors</subject><subject>chemical irritant</subject><subject>cough</subject><subject>Fibers</subject><subject>Inhalation</subject><subject>Ion channels</subject><subject>Lung</subject><subject>lung injury</subject><subject>Mice</subject><subject>Nerve Fibers, Unmyelinated</subject><subject>Perfusion</subject><subject>Rats</subject><subject>Sensory neurons</subject><subject>Sodium bicarbonate</subject><subject>Sulfur</subject><subject>Sulfur dioxide</subject><subject>Sulfur Dioxide - toxicity</subject><subject>Transient receptor potential proteins</subject><subject>TRPV Cation Channels</subject><subject>TRPV1</subject><subject>Vagus Nerve</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9u1DAQxi0EosuCxBMgS1y4pPhPEscXJLTiT6tW9FDOlhOPNy6OvdhJYW88As_Ik-Bq2woOPc1hfvPNN_Mh9JKSY0opf3t6wYSkDXuEVrRuZSWE5I_RihDGKi4aeoSe5XxFCOVEyqfoiNNOUir5Cn07h2HUweUp4yUYSH7vwhbPI-A8u2nxeo5pj8FaGGYcLXZh1B4Mzou3S8LGxZ_OAI4BX-ut9rhPMQxj3C1-ikGX0c2fX7-t6xPk5-iJ1T7Di9u6Rl8_frjcfK7Ovnw62bw_q4aay7bqasGMbnlnoGuspaSnYEQtwJCaGi2N5Z2uW1ouBVHQcrcUvem1ZDUjfc_X6N1Bd7f0E5gBwpy0V7vkpmJIRe3U_53gRrWN10qQpqxgReD1rUCK3xfIs7qKSwrFs2K8bTrBWHneGr05UEOKOSew9xsoUTexqLtYCvrqX0f34F0OBTg-AD-ch_2DQury9IJy2bT8L-XgmQc</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Lin, An‐Hsuan</creator><creator>Hsu, Chun‐Chun</creator><creator>Lin, You Shuei</creator><creator>Lin, Ruei‐Lung</creator><creator>Lee, Lu‐Yuan</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TS</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8545-2222</orcidid><orcidid>https://orcid.org/0000-0001-8306-2845</orcidid></search><sort><creationdate>20200301</creationdate><title>Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C‐fibres</title><author>Lin, An‐Hsuan ; Hsu, Chun‐Chun ; Lin, You Shuei ; Lin, Ruei‐Lung ; Lee, Lu‐Yuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4396-8472da638de85ff10b1ed747ed041da9df38a461146e772d15297bdba92420bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acidification</topic><topic>Acidosis</topic><topic>Amiloride</topic><topic>Animals</topic><topic>ASIC</topic><topic>Bronchi</topic><topic>Bronchoconstriction</topic><topic>Calcium (intracellular)</topic><topic>Capsaicin receptors</topic><topic>chemical irritant</topic><topic>cough</topic><topic>Fibers</topic><topic>Inhalation</topic><topic>Ion channels</topic><topic>Lung</topic><topic>lung injury</topic><topic>Mice</topic><topic>Nerve Fibers, Unmyelinated</topic><topic>Perfusion</topic><topic>Rats</topic><topic>Sensory neurons</topic><topic>Sodium bicarbonate</topic><topic>Sulfur</topic><topic>Sulfur dioxide</topic><topic>Sulfur Dioxide - toxicity</topic><topic>Transient receptor potential proteins</topic><topic>TRPV Cation Channels</topic><topic>TRPV1</topic><topic>Vagus Nerve</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, An‐Hsuan</creatorcontrib><creatorcontrib>Hsu, Chun‐Chun</creatorcontrib><creatorcontrib>Lin, You Shuei</creatorcontrib><creatorcontrib>Lin, Ruei‐Lung</creatorcontrib><creatorcontrib>Lee, Lu‐Yuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, An‐Hsuan</au><au>Hsu, Chun‐Chun</au><au>Lin, You Shuei</au><au>Lin, Ruei‐Lung</au><au>Lee, Lu‐Yuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C‐fibres</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>598</volume><issue>5</issue><spage>1093</spage><epage>1108</epage><pages>1093-1108</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><abstract>Key points
Brief inhalation of SO2 of concentration >500 p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C‐fibres in anaesthetized rats.
This stimulatory effect was drastically diminished by a pretreatment with NaHCO3 that raised the baseline arterial pH, suggesting a possible involvement of acidification of airway fluid and/or tissue generated by inhaled SO2.
The stimulation was completely abolished by pretreatment with antagonists of both acid‐sensing ion channels and transient receptor potential vanilloid type‐1 receptors, indicating that this effect was caused by acid activation of these cation channels expressed in airway sensory nerves.
This conclusion was further supported by the results obtained from studies in isolated rat vagal bronchopulmonary sensory neurones and also in the cough response to SO2 inhalation challenge in awake mice.
These results provide new insight into the underlying mechanism of harmful irritant effects in the respiratory tract caused by accidental exposure to a high concentration of SO2.
Inhalation of sulfur dioxide (SO2) triggers coughs and reflex bronchoconstriction, and stimulation of vagal bronchopulmonary C‐fibres is primarily responsible. However, the mechanism underlying this stimulatory effect is not yet fully understood. In this study, we tested the hypothesis that the C‐fibre stimulation was caused by SO2‐induced local tissue acidosis in the lung and airways. Single‐unit activities of bronchopulmonary C‐fibres in response to inhalation challenges of SO2 (500–1500 p.p.m., 10 breaths) were measured in anaesthetized rats. Inhalation of SO2 reproducibly induced a pronounced and sustained stimulation (lasting for 15–60 s) of pulmonary C‐fibres in a concentration‐dependent manner. This stimulatory effect was significantly attenuated by an increase in arterial pH generated by infusion of sodium bicarbonate (NaHCO3), and completely abrogated by a combined pretreatment with amiloride (an antagonist of acid‐sensing ion channels, ASICs) and AMG8910 (a selective antagonist of the transient receptor potential vanilloid type‐1 receptor, TRPV1). Furthermore, in isolated rat vagal pulmonary sensory neurones, perfusion of an aqueous solution of SO2 evoked a transient increase in the intracellular Ca2+ concentration; this response was also markedly diminished by a pretreatment with amiloride and AMG8910. In addition, inhalation of SO2 consistently evoked coughs in awake mice; responses were significantly smaller in TRPV1−/− mice than in wild‐type mice, and almost completely abolished after a pretreatment with amiloride in TRPV1−/− mice. These results suggested that the stimulatory effect of inhaled SO2 on bronchopulmonary C‐fibres was generated by acidification of fluid and/or tissue in the lung and airways, which activated both ASICs and TRPV1 expressed in these sensory nerves.
Key points
Brief inhalation of SO2 of concentration >500 p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C‐fibres in anaesthetized rats.
This stimulatory effect was drastically diminished by a pretreatment with NaHCO3 that raised the baseline arterial pH, suggesting a possible involvement of acidification of airway fluid and/or tissue generated by inhaled SO2.
The stimulation was completely abolished by pretreatment with antagonists of both acid‐sensing ion channels and transient receptor potential vanilloid type‐1 receptors, indicating that this effect was caused by acid activation of these cation channels expressed in airway sensory nerves.
This conclusion was further supported by the results obtained from studies in isolated rat vagal bronchopulmonary sensory neurones and also in the cough response to SO2 inhalation challenge in awake mice.
These results provide new insight into the underlying mechanism of harmful irritant effects in the respiratory tract caused by accidental exposure to a high concentration of SO2.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31891193</pmid><doi>10.1113/JP279152</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-8545-2222</orcidid><orcidid>https://orcid.org/0000-0001-8306-2845</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3751 |
| ispartof | The Journal of physiology, 2020-03, Vol.598 (5), p.1093-1108 |
| issn | 0022-3751 1469-7793 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7050412 |
| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Acidification Acidosis Amiloride Animals ASIC Bronchi Bronchoconstriction Calcium (intracellular) Capsaicin receptors chemical irritant cough Fibers Inhalation Ion channels Lung lung injury Mice Nerve Fibers, Unmyelinated Perfusion Rats Sensory neurons Sodium bicarbonate Sulfur Sulfur dioxide Sulfur Dioxide - toxicity Transient receptor potential proteins TRPV Cation Channels TRPV1 Vagus Nerve |
| title | Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C‐fibres |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T07%3A38%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mechanisms%20underlying%20the%20stimulatory%20effect%20of%20inhaled%20sulfur%20dioxide%20on%20vagal%20bronchopulmonary%20C%E2%80%90fibres&rft.jtitle=The%20Journal%20of%20physiology&rft.au=Lin,%20An%E2%80%90Hsuan&rft.date=2020-03-01&rft.volume=598&rft.issue=5&rft.spage=1093&rft.epage=1108&rft.pages=1093-1108&rft.issn=0022-3751&rft.eissn=1469-7793&rft_id=info:doi/10.1113/JP279152&rft_dat=%3Cproquest_pubme%3E2365872219%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2365872219&rft_id=info:pmid/31891193&rfr_iscdi=true |