Relaxant Action of Diclofenac Sodium on Mouse Airway Smooth Muscle
Identifieur interne : 000568 ( Pmc/Curation ); précédent : 000567; suivant : 000569Relaxant Action of Diclofenac Sodium on Mouse Airway Smooth Muscle
Auteurs : Chunfa Chen [République populaire de Chine] ; Yongle Yang [République populaire de Chine] ; Meng-Fei Yu [République populaire de Chine] ; Shunbo Shi [République populaire de Chine] ; Shuhui Han [République populaire de Chine] ; Qing-Hua Liu [République populaire de Chine] ; Congli Cai [République populaire de Chine] ; Jinhua Shen [République populaire de Chine]Source :
- Frontiers in Pharmacology [ 1663-9812 ] ; 2019.
Abstract
Diclofenac sodium (DCF) is a nonsteroidal anti-inflammatory drug (NSAID) and is widely used as an analgesic and anti-inflammatory agent. Herein, we found that DCF could relax high K+ (80 mM K+)-/ACh-precontracted tracheal rings (TRs) in mice. This study aimed to elucidate the underlying mechanisms of DCF-induced relaxations. The effects of DCF on airway smooth muscle (ASM) cells were explored using multiple biophysiological techniques, such as isometric tension measurement and patch-clamping experiments. Both high K+- and ACh-evoked contraction of TRs in mice were relaxed by DCF in a dose-dependent manner. The results of isometric tension and patch-clamping experiments demonstrated that DCF-induced relaxation in ASM cells was mediated by cytosolic free Ca2+, which was decreased via inhibition of voltage-dependent L-type Ca2+ channels (VDLCCs), nonselective cation channels (NSCCs), and Na+/Ca2+ exchange. Meanwhile, DCF also enhanced large conductance Ca2+ activated K+ (BK) channels, which led to the relaxation of ASMs. Our data demonstrated that DCF relaxed ASMs by decreasing the intracellular Ca2+ concentration via inhibition of Ca2+ influx and Na+/Ca2+ exchange. Meanwhile, the enhanced BK channels also played a role in DCF-induced relaxation in ASMs. These results suggest that DCF is a potential candidate for antibronchospasmic drugs used in treating respiratory diseases such as asthma and chronic obstructive pulmonary disease.
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DOI: 10.3389/fphar.2019.00608
PubMed: 31275141
PubMed Central: 6591797
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Relaxant Action of Diclofenac Sodium on Mouse Airway Smooth Muscle</title><author><name sortKey="Chen, Chunfa" sort="Chen, Chunfa" uniqKey="Chen C" first="Chunfa" last="Chen">Chunfa Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Yongle" sort="Yang, Yongle" uniqKey="Yang Y" first="Yongle" last="Yang">Yongle Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yu, Meng Fei" sort="Yu, Meng Fei" uniqKey="Yu M" first="Meng-Fei" last="Yu">Meng-Fei Yu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Shunbo" sort="Shi, Shunbo" uniqKey="Shi S" first="Shunbo" last="Shi">Shunbo Shi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Han, Shuhui" sort="Han, Shuhui" uniqKey="Han S" first="Shuhui" last="Han">Shuhui Han</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Qing Hua" sort="Liu, Qing Hua" uniqKey="Liu Q" first="Qing-Hua" last="Liu">Qing-Hua Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cai, Congli" sort="Cai, Congli" uniqKey="Cai C" first="Congli" last="Cai">Congli Cai</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Molecular Biology, Wuhan Youzhiyou Biopharmaceutical Co. 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type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591797</idno><idno type="RBID">PMC:6591797</idno><idno type="doi">10.3389/fphar.2019.00608</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000568</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000568</idno><idno type="wicri:Area/Pmc/Curation">000568</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000568</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Relaxant Action of Diclofenac Sodium on Mouse Airway Smooth Muscle</title><author><name sortKey="Chen, Chunfa" sort="Chen, Chunfa" uniqKey="Chen C" first="Chunfa" last="Chen">Chunfa Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Yongle" sort="Yang, Yongle" uniqKey="Yang Y" first="Yongle" last="Yang">Yongle Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yu, Meng Fei" sort="Yu, Meng Fei" uniqKey="Yu M" first="Meng-Fei" last="Yu">Meng-Fei Yu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Shunbo" sort="Shi, Shunbo" uniqKey="Shi S" first="Shunbo" last="Shi">Shunbo Shi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Han, Shuhui" sort="Han, Shuhui" uniqKey="Han S" first="Shuhui" last="Han">Shuhui Han</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Qing Hua" sort="Liu, Qing Hua" uniqKey="Liu Q" first="Qing-Hua" last="Liu">Qing-Hua Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cai, Congli" sort="Cai, Congli" uniqKey="Cai C" first="Congli" last="Cai">Congli Cai</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Molecular Biology, Wuhan Youzhiyou Biopharmaceutical Co. Ltd.</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shen, Jinhua" sort="Shen, Jinhua" uniqKey="Shen J" first="Jinhua" last="Shen">Jinhua Shen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Pharmacology</title><idno type="eISSN">1663-9812</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Diclofenac sodium (DCF) is a nonsteroidal anti-inflammatory drug (NSAID) and is widely used as an analgesic and anti-inflammatory agent. Herein, we found that DCF could relax high K<sup>+</sup> (80 mM K<sup>+</sup>)-/ACh-precontracted tracheal rings (TRs) in mice. This study aimed to elucidate the underlying mechanisms of DCF-induced relaxations. The effects of DCF on airway smooth muscle (ASM) cells were explored using multiple biophysiological techniques, such as isometric tension measurement and patch-clamping experiments. Both high K<sup>+</sup>- and ACh-evoked contraction of TRs in mice were relaxed by DCF in a dose-dependent manner. The results of isometric tension and patch-clamping experiments demonstrated that DCF-induced relaxation in ASM cells was mediated by cytosolic free Ca<sup>2+</sup>, which was decreased via inhibition of voltage-dependent L-type Ca<sup>2+</sup> channels (VDLCCs), nonselective cation channels (NSCCs), and Na<sup>+/</sup>Ca<sup>2+</sup> exchange. Meanwhile, DCF also enhanced large conductance Ca<sup>2+</sup> activated K<sup>+</sup> (BK) channels, which led to the relaxation of ASMs. Our data demonstrated that DCF relaxed ASMs by decreasing the intracellular Ca<sup>2+</sup> concentration via inhibition of Ca<sup>2+</sup> influx and Na<sup>+</sup>/Ca<sup>2+</sup> exchange. Meanwhile, the enhanced BK channels also played a role in DCF-induced relaxation in ASMs. These results suggest that DCF is a potential candidate for antibronchospasmic drugs used in treating respiratory diseases such as asthma and chronic obstructive pulmonary disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Adams, N P" uniqKey="Adams N">N. P. Adams</name></author><author><name sortKey="Jones, P W" uniqKey="Jones P">P. W. Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arumugam, A" uniqKey="Arumugam A">A. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Pharmacol</journal-id><journal-id journal-id-type="iso-abbrev">Front Pharmacol</journal-id><journal-id journal-id-type="publisher-id">Front. Pharmacol.</journal-id><journal-title-group><journal-title>Frontiers in Pharmacology</journal-title></journal-title-group><issn pub-type="epub">1663-9812</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31275141</article-id><article-id pub-id-type="pmc">6591797</article-id><article-id pub-id-type="doi">10.3389/fphar.2019.00608</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject><subj-group><subject>Original Research</subject></subj-group></subj-group></article-categories><title-group><article-title>Relaxant Action of Diclofenac Sodium on Mouse Airway Smooth Muscle</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Chunfa</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn003"><sup>†</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/713207"></uri></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Yongle</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn003"><sup>†</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/748762"></uri></contrib><contrib contrib-type="author"><name><surname>Yu</surname><given-names>Meng-Fei</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn003"><sup>†</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/688116"></uri></contrib><contrib contrib-type="author"><name><surname>Shi</surname><given-names>Shunbo</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/748759"></uri></contrib><contrib contrib-type="author"><name><surname>Han</surname><given-names>Shuhui</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/748761"></uri></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Qing-hua</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/736658"></uri></contrib><contrib contrib-type="author"><name><surname>Cai</surname><given-names>Congli</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/748760"></uri></contrib><contrib contrib-type="author"><name><surname>Shen</surname><given-names>Jinhua</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn001"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/748770"></uri></contrib></contrib-group><aff id="aff1"><sup>1</sup><institution>Institute for Medical Biology, Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></aff><aff id="aff2"><sup>2</sup><institution>Department of Molecular Biology, Wuhan Youzhiyou Biopharmaceutical Co. Ltd.</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Giuseppa Pistritto, Agenzia Italiana del farmaco (AIFA), Italy</p></fn><fn fn-type="edited-by"><p>Reviewed by: Sathish Venkatachalem, North Dakota State University, United States; Vaidehi Jatin Thanawala, Vapogenix Inc, United States</p></fn><corresp id="fn001">*Correspondence: Jinhua Shen, <email xlink:href="mailto:shenjinhua2013@163.com" xlink:type="simple">shenjinhua2013@163.com</email>, <email xlink:href="mailto:2011084@mail.scuec.edu.cn" xlink:type="simple">2011084@mail.scuec.edu.cn</email></corresp><fn fn-type="other" id="fn002"><p>This article was submitted to Respiratory Pharmacology, a section of the journal Frontiers in Pharmacology</p></fn><fn fn-type="equal" id="fn003"><p>†These authors have contributed equally to this work.</p></fn></author-notes><pub-date pub-type="epub"><day>18</day><month>6</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>10</volume><elocation-id>608</elocation-id><history><date date-type="received"><day>15</day><month>2</month><year>2019</year></date><date date-type="accepted"><day>14</day><month>5</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019 Chen, Yang, Yu, Shi, Han, Liu, Cai and Shen</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>Chen, Yang, Yu, Shi, Han, Liu, Cai and Shen</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><p>Diclofenac sodium (DCF) is a nonsteroidal anti-inflammatory drug (NSAID) and is widely used as an analgesic and anti-inflammatory agent. Herein, we found that DCF could relax high K<sup>+</sup> (80 mM K<sup>+</sup>)-/ACh-precontracted tracheal rings (TRs) in mice. This study aimed to elucidate the underlying mechanisms of DCF-induced relaxations. The effects of DCF on airway smooth muscle (ASM) cells were explored using multiple biophysiological techniques, such as isometric tension measurement and patch-clamping experiments. Both high K<sup>+</sup>- and ACh-evoked contraction of TRs in mice were relaxed by DCF in a dose-dependent manner. The results of isometric tension and patch-clamping experiments demonstrated that DCF-induced relaxation in ASM cells was mediated by cytosolic free Ca<sup>2+</sup>, which was decreased via inhibition of voltage-dependent L-type Ca<sup>2+</sup> channels (VDLCCs), nonselective cation channels (NSCCs), and Na<sup>+/</sup>Ca<sup>2+</sup> exchange. Meanwhile, DCF also enhanced large conductance Ca<sup>2+</sup> activated K<sup>+</sup> (BK) channels, which led to the relaxation of ASMs. Our data demonstrated that DCF relaxed ASMs by decreasing the intracellular Ca<sup>2+</sup> concentration via inhibition of Ca<sup>2+</sup> influx and Na<sup>+</sup>/Ca<sup>2+</sup> exchange. Meanwhile, the enhanced BK channels also played a role in DCF-induced relaxation in ASMs. These results suggest that DCF is a potential candidate for antibronchospasmic drugs used in treating respiratory diseases such as asthma and chronic obstructive pulmonary disease.</p></abstract><kwd-group><kwd>airway smooth muscle</kwd><kwd>BK channels</kwd><kwd>diclofenac sodium</kwd><kwd>relaxation</kwd><kwd>tracheal rings</kwd><kwd>voltage-dependent Ca<sup>2+</sup> channels</kwd></kwd-group><counts><fig-count count="14"></fig-count><table-count count="0"></table-count><equation-count count="0"></equation-count><ref-count count="53"></ref-count><page-count count="16"></page-count><word-count count="6232"></word-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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