Inhibition of Rho-kinase normalizes nonspecific hyperresponsiveness in passively sensitized airway smooth muscle preparations
Currently, little is known about mechanisms underlying passive sensitization-induced nonspecific airway hyperresponsiveness. We sought to determine whether the nonspecific airway hyperresponsiveness observed after passive sensitization involves an increased role of Rho-kinase in airway smooth muscle...
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| Veröffentlicht in: | European journal of pharmacology 2006-02, Vol.531 (1), p.145-150 |
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| creator | Schaafsma, Dedmer Zuidhof, Annet B. Nelemans, S.A. Zaagsma, Johan Meurs, Herman |
| description | Currently, little is known about mechanisms underlying passive sensitization-induced nonspecific airway hyperresponsiveness. We sought to determine whether the nonspecific airway hyperresponsiveness observed after passive sensitization involves an increased role of Rho-kinase in airway smooth muscle contraction. In addition, the contribution of Rho-kinase to specific allergen-induced airway smooth muscle contraction was studied. Guinea pig tracheal smooth muscle preparations were incubated for 16 h, in the presence of serum obtained from nonsensitized guinea pigs or atopic serum obtained from actively ovalbumin-sensitized guinea pigs. After incubation, the contribution of Rho-kinase to histamine-, methacholine- or ovalbumin-induced isometric contractions was determined, using the specific Rho-kinase inhibitor Y-27632.
Maximal contractions induced by histamine and methacholine were significantly increased in passively sensitized preparations, without a change in potency (−
logEC
50). In control preparations, Y-27632 reduced the potency of both agonists, without affecting maximal contraction. Remarkably, the increased agonist responsiveness induced by passive sensitization was fully normalized by Y-27632. Treatment with Y-27632 also reduced ovalbumin-induced contraction in these preparations.
This study shows that the nonspecific airway smooth muscle hyperresponsiveness as well as the specific allergen responsiveness induced by passive sensitization are dependent on Rho-kinase. The complete inhibition by Y-27632 of the passive sensitization-induced increased responsiveness toward histamine and methacholine indicates a pivotal role of Rho-kinase in this process. |
| doi_str_mv | 10.1016/j.ejphar.2005.12.043 |
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Maximal contractions induced by histamine and methacholine were significantly increased in passively sensitized preparations, without a change in potency (−
logEC
50). In control preparations, Y-27632 reduced the potency of both agonists, without affecting maximal contraction. Remarkably, the increased agonist responsiveness induced by passive sensitization was fully normalized by Y-27632. Treatment with Y-27632 also reduced ovalbumin-induced contraction in these preparations.
This study shows that the nonspecific airway smooth muscle hyperresponsiveness as well as the specific allergen responsiveness induced by passive sensitization are dependent on Rho-kinase. The complete inhibition by Y-27632 of the passive sensitization-induced increased responsiveness toward histamine and methacholine indicates a pivotal role of Rho-kinase in this process.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2005.12.043</identifier><identifier>PMID: 16451800</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Airway hyperresponsiveness ; Airway smooth muscle ; Allergy ; Amides - pharmacology ; Animals ; Asthma ; Biological and medical sciences ; Chronic obstructive pulmonary disease, asthma ; Contraction ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - pharmacology ; Guinea pig ; Guinea Pigs ; Histamine - pharmacology ; In Vitro Techniques ; Intracellular Signaling Peptides and Proteins ; Male ; Medical sciences ; Methacholine Chloride - pharmacology ; Muscle Contraction - drug effects ; Muscle, Smooth - drug effects ; Muscle, Smooth - immunology ; Muscle, Smooth - physiology ; Ovalbumin ; Ovalbumin - immunology ; Passive sensitization ; Pharmacology. Drug treatments ; Pneumology ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Pyridines - pharmacology ; rho-Associated Kinases ; Rho-kinase ; Time Factors ; Trachea - drug effects ; Trachea - immunology ; Trachea - physiology ; Y-27632</subject><ispartof>European journal of pharmacology, 2006-02, Vol.531 (1), p.145-150</ispartof><rights>2005 Elsevier B.V.</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-a460d157a9d5bf0dc3704bc2f8b6943dc075208cd90e1f375b2bd501a16bf903</citedby><cites>FETCH-LOGICAL-c390t-a460d157a9d5bf0dc3704bc2f8b6943dc075208cd90e1f375b2bd501a16bf903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2005.12.043$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17495445$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16451800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schaafsma, Dedmer</creatorcontrib><creatorcontrib>Zuidhof, Annet B.</creatorcontrib><creatorcontrib>Nelemans, S.A.</creatorcontrib><creatorcontrib>Zaagsma, Johan</creatorcontrib><creatorcontrib>Meurs, Herman</creatorcontrib><title>Inhibition of Rho-kinase normalizes nonspecific hyperresponsiveness in passively sensitized airway smooth muscle preparations</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Currently, little is known about mechanisms underlying passive sensitization-induced nonspecific airway hyperresponsiveness. We sought to determine whether the nonspecific airway hyperresponsiveness observed after passive sensitization involves an increased role of Rho-kinase in airway smooth muscle contraction. In addition, the contribution of Rho-kinase to specific allergen-induced airway smooth muscle contraction was studied. Guinea pig tracheal smooth muscle preparations were incubated for 16 h, in the presence of serum obtained from nonsensitized guinea pigs or atopic serum obtained from actively ovalbumin-sensitized guinea pigs. After incubation, the contribution of Rho-kinase to histamine-, methacholine- or ovalbumin-induced isometric contractions was determined, using the specific Rho-kinase inhibitor Y-27632.
Maximal contractions induced by histamine and methacholine were significantly increased in passively sensitized preparations, without a change in potency (−
logEC
50). In control preparations, Y-27632 reduced the potency of both agonists, without affecting maximal contraction. Remarkably, the increased agonist responsiveness induced by passive sensitization was fully normalized by Y-27632. Treatment with Y-27632 also reduced ovalbumin-induced contraction in these preparations.
This study shows that the nonspecific airway smooth muscle hyperresponsiveness as well as the specific allergen responsiveness induced by passive sensitization are dependent on Rho-kinase. The complete inhibition by Y-27632 of the passive sensitization-induced increased responsiveness toward histamine and methacholine indicates a pivotal role of Rho-kinase in this process.</description><subject>Airway hyperresponsiveness</subject><subject>Airway smooth muscle</subject><subject>Allergy</subject><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Asthma</subject><subject>Biological and medical sciences</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>Contraction</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Guinea pig</subject><subject>Guinea Pigs</subject><subject>Histamine - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methacholine Chloride - pharmacology</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle, Smooth - drug effects</subject><subject>Muscle, Smooth - immunology</subject><subject>Muscle, Smooth - physiology</subject><subject>Ovalbumin</subject><subject>Ovalbumin - immunology</subject><subject>Passive sensitization</subject><subject>Pharmacology. Drug treatments</subject><subject>Pneumology</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Pyridines - pharmacology</subject><subject>rho-Associated Kinases</subject><subject>Rho-kinase</subject><subject>Time Factors</subject><subject>Trachea - drug effects</subject><subject>Trachea - immunology</subject><subject>Trachea - physiology</subject><subject>Y-27632</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kN-L1DAQx4Mo3nr6H4jkRd9aJ23Sbl4EOfxxcCDIvYc0mdKsbVoz3TtW8H83ZRfuzackk893Zvgw9lZAKUA0Hw8lHpbBprICUKWoSpD1M7YT-1YX0IrqOdsBCFlUWusr9oroABnUlXrJrkQjldgD7Njf2ziELqxhjnzu-c9hLn6FaAl5nNNkx_AHKV8jLehCHxwfTgumhLTkWnjAiEQ8RL5Y2p7jiRPmjzXnPLchPdpcmeZ5Hfh0JDciXxIuNtltIr1mL3o7Er65nNfs_uuX-5vvxd2Pb7c3n-8KV2tYCysb8EK1VnvV9eBd3YLsXNXvu0bL2jtoVQV75zWg6OtWdVXnFQgrmq7XUF-zD-e2S5p_H5FWMwVyOI424nwk07SNqve1yqA8gy7NRAl7s6Qw2XQyAsxm3RzM2brZrBtRmWw9x95d-h-7Cf1T6KI5A-8vgCVnxz7Z6AI9ca3USspt_qczh1nGQ8BkyAWMDn1I6Fbj5_D_Tf4B6vqmTQ</recordid><startdate>20060215</startdate><enddate>20060215</enddate><creator>Schaafsma, Dedmer</creator><creator>Zuidhof, Annet B.</creator><creator>Nelemans, S.A.</creator><creator>Zaagsma, Johan</creator><creator>Meurs, Herman</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20060215</creationdate><title>Inhibition of Rho-kinase normalizes nonspecific hyperresponsiveness in passively sensitized airway smooth muscle preparations</title><author>Schaafsma, Dedmer ; Zuidhof, Annet B. ; Nelemans, S.A. ; Zaagsma, Johan ; Meurs, Herman</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-a460d157a9d5bf0dc3704bc2f8b6943dc075208cd90e1f375b2bd501a16bf903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Airway hyperresponsiveness</topic><topic>Airway smooth muscle</topic><topic>Allergy</topic><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Asthma</topic><topic>Biological and medical sciences</topic><topic>Chronic obstructive pulmonary disease, asthma</topic><topic>Contraction</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Guinea pig</topic><topic>Guinea Pigs</topic><topic>Histamine - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methacholine Chloride - pharmacology</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle, Smooth - drug effects</topic><topic>Muscle, Smooth - immunology</topic><topic>Muscle, Smooth - physiology</topic><topic>Ovalbumin</topic><topic>Ovalbumin - immunology</topic><topic>Passive sensitization</topic><topic>Pharmacology. Drug treatments</topic><topic>Pneumology</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Pyridines - pharmacology</topic><topic>rho-Associated Kinases</topic><topic>Rho-kinase</topic><topic>Time Factors</topic><topic>Trachea - drug effects</topic><topic>Trachea - immunology</topic><topic>Trachea - physiology</topic><topic>Y-27632</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schaafsma, Dedmer</creatorcontrib><creatorcontrib>Zuidhof, Annet B.</creatorcontrib><creatorcontrib>Nelemans, S.A.</creatorcontrib><creatorcontrib>Zaagsma, Johan</creatorcontrib><creatorcontrib>Meurs, Herman</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schaafsma, Dedmer</au><au>Zuidhof, Annet B.</au><au>Nelemans, S.A.</au><au>Zaagsma, Johan</au><au>Meurs, Herman</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Rho-kinase normalizes nonspecific hyperresponsiveness in passively sensitized airway smooth muscle preparations</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2006-02-15</date><risdate>2006</risdate><volume>531</volume><issue>1</issue><spage>145</spage><epage>150</epage><pages>145-150</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>Currently, little is known about mechanisms underlying passive sensitization-induced nonspecific airway hyperresponsiveness. We sought to determine whether the nonspecific airway hyperresponsiveness observed after passive sensitization involves an increased role of Rho-kinase in airway smooth muscle contraction. In addition, the contribution of Rho-kinase to specific allergen-induced airway smooth muscle contraction was studied. Guinea pig tracheal smooth muscle preparations were incubated for 16 h, in the presence of serum obtained from nonsensitized guinea pigs or atopic serum obtained from actively ovalbumin-sensitized guinea pigs. After incubation, the contribution of Rho-kinase to histamine-, methacholine- or ovalbumin-induced isometric contractions was determined, using the specific Rho-kinase inhibitor Y-27632.
Maximal contractions induced by histamine and methacholine were significantly increased in passively sensitized preparations, without a change in potency (−
logEC
50). In control preparations, Y-27632 reduced the potency of both agonists, without affecting maximal contraction. Remarkably, the increased agonist responsiveness induced by passive sensitization was fully normalized by Y-27632. Treatment with Y-27632 also reduced ovalbumin-induced contraction in these preparations.
This study shows that the nonspecific airway smooth muscle hyperresponsiveness as well as the specific allergen responsiveness induced by passive sensitization are dependent on Rho-kinase. The complete inhibition by Y-27632 of the passive sensitization-induced increased responsiveness toward histamine and methacholine indicates a pivotal role of Rho-kinase in this process.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>16451800</pmid><doi>10.1016/j.ejphar.2005.12.043</doi><tpages>6</tpages></addata></record> |
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| ispartof | European journal of pharmacology, 2006-02, Vol.531 (1), p.145-150 |
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| subjects | Airway hyperresponsiveness Airway smooth muscle Allergy Amides - pharmacology Animals Asthma Biological and medical sciences Chronic obstructive pulmonary disease, asthma Contraction Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology Guinea pig Guinea Pigs Histamine - pharmacology In Vitro Techniques Intracellular Signaling Peptides and Proteins Male Medical sciences Methacholine Chloride - pharmacology Muscle Contraction - drug effects Muscle, Smooth - drug effects Muscle, Smooth - immunology Muscle, Smooth - physiology Ovalbumin Ovalbumin - immunology Passive sensitization Pharmacology. Drug treatments Pneumology Protein-Serine-Threonine Kinases - antagonists & inhibitors Pyridines - pharmacology rho-Associated Kinases Rho-kinase Time Factors Trachea - drug effects Trachea - immunology Trachea - physiology Y-27632 |
| title | Inhibition of Rho-kinase normalizes nonspecific hyperresponsiveness in passively sensitized airway smooth muscle preparations |
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