Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs
Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with re...
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| description | Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01). Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001). In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known. |
| doi_str_mv | 10.1371/journal.pone.0119953 |
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Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01). Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001). In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0119953</identifier><identifier>PMID: 25781609</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Adrenergic beta-2 Receptor Agonists - administration & dosage ; Adrenergic beta-2 Receptor Agonists - therapeutic use ; Adrenergic receptors ; Animals ; Antitussive Agents - administration & dosage ; Antitussive Agents - therapeutic use ; Benzoxazines - administration & dosage ; Benzoxazines - therapeutic use ; Bronchodilation ; Bronchodilators ; Chronic obstructive pulmonary disease ; Citric Acid ; Cough ; Cough - chemically induced ; Cough - drug therapy ; Disease ; Drug Evaluation, Preclinical ; Effectiveness ; Exposure ; Formoterol ; Guinea Pigs ; Hyperpolarization ; Inhalation ; Kinases ; Lungs ; Male ; Molecular modelling ; Neurons ; Ovalbumin ; Powder ; Properties (attributes) ; Receptors ; Receptors (physiology) ; Respiration ; Respiratory diseases ; Respiratory tract diseases ; Rodents ; Salmeterol</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0119953-e0119953</ispartof><rights>2015 Wex, Bouyssou. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Wex, Bouyssou 2015 Wex, Bouyssou</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-ff7f801fb22c21d1e3cd379485e3f122980a3f6b5b985a0552efda84a42ecb033</citedby><cites>FETCH-LOGICAL-c526t-ff7f801fb22c21d1e3cd379485e3f122980a3f6b5b985a0552efda84a42ecb033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364307/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364307/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25781609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wex, Eva</creatorcontrib><creatorcontrib>Bouyssou, Thierry</creatorcontrib><title>Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01). Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001). In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known.</description><subject>Acids</subject><subject>Adrenergic beta-2 Receptor Agonists - administration & dosage</subject><subject>Adrenergic beta-2 Receptor Agonists - therapeutic use</subject><subject>Adrenergic receptors</subject><subject>Animals</subject><subject>Antitussive Agents - administration & dosage</subject><subject>Antitussive Agents - therapeutic use</subject><subject>Benzoxazines - administration & dosage</subject><subject>Benzoxazines - therapeutic use</subject><subject>Bronchodilation</subject><subject>Bronchodilators</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Citric Acid</subject><subject>Cough</subject><subject>Cough - chemically induced</subject><subject>Cough - drug therapy</subject><subject>Disease</subject><subject>Drug Evaluation, Preclinical</subject><subject>Effectiveness</subject><subject>Exposure</subject><subject>Formoterol</subject><subject>Guinea Pigs</subject><subject>Hyperpolarization</subject><subject>Inhalation</subject><subject>Kinases</subject><subject>Lungs</subject><subject>Male</subject><subject>Molecular modelling</subject><subject>Neurons</subject><subject>Ovalbumin</subject><subject>Powder</subject><subject>Properties (attributes)</subject><subject>Receptors</subject><subject>Receptors (physiology)</subject><subject>Respiration</subject><subject>Respiratory diseases</subject><subject>Respiratory tract diseases</subject><subject>Rodents</subject><subject>Salmeterol</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptkstu1DAUhiMEoqXwBggisWGTwZfEdjZIqOJSqVI3sLZO7OOMRx57sJOR4KV4CF6MDDOtWsTKl_P9v8-x_qp6ScmKcknfbdKcI4TVLkVcEUr7vuOPqnPac9YIRvjje_uz6lkpG0I6roR4Wp2xTioqSH9ebW9CsjBhTqGGacI4L4dSGz9lb2ow3jY-2tmgrU2ax3XtYx3h96891hBtnfYQhnnrY1MwFj_5nwt4KJg1hIBxXI7j7CNCvfNjeV49cRAKvjitF9W3Tx-_Xn5prm8-X11-uG5Mx8TUOCedItQNjBlGLUVuLJd9qzrkjjLWKwLciaEbetUB6TqGzoJqoWVoBsL5RfX66LsLqejTTxVNhWgZk4toIa6OhE2w0bvst5B_6ARe_71IedSQJ28CaiMMMqeYRCtbqSwQxgfqXKsMB94Ni9f702vzsEVrME4ZwgPTh5Xo13pMe91y0XIiF4O3J4Ocvs9YJr31xWAIEDHNx76lFD1RC_rmH_T_07VHyuRUSkZ31wwl-pCeW5U-pEef0rPIXt0f5E50Gxf-B0p-xgU</recordid><startdate>20150317</startdate><enddate>20150317</enddate><creator>Wex, Eva</creator><creator>Bouyssou, Thierry</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150317</creationdate><title>Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs</title><author>Wex, Eva ; Bouyssou, Thierry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-ff7f801fb22c21d1e3cd379485e3f122980a3f6b5b985a0552efda84a42ecb033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acids</topic><topic>Adrenergic beta-2 Receptor Agonists - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wex, Eva</au><au>Bouyssou, Thierry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-17</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0119953</spage><epage>e0119953</epage><pages>e0119953-e0119953</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01). Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001). In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25781609</pmid><doi>10.1371/journal.pone.0119953</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Acids Adrenergic beta-2 Receptor Agonists - administration & dosage Adrenergic beta-2 Receptor Agonists - therapeutic use Adrenergic receptors Animals Antitussive Agents - administration & dosage Antitussive Agents - therapeutic use Benzoxazines - administration & dosage Benzoxazines - therapeutic use Bronchodilation Bronchodilators Chronic obstructive pulmonary disease Citric Acid Cough Cough - chemically induced Cough - drug therapy Disease Drug Evaluation, Preclinical Effectiveness Exposure Formoterol Guinea Pigs Hyperpolarization Inhalation Kinases Lungs Male Molecular modelling Neurons Ovalbumin Powder Properties (attributes) Receptors Receptors (physiology) Respiration Respiratory diseases Respiratory tract diseases Rodents Salmeterol |
| title | Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs |
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