Why do asthmatic subjects respond so strongly to inhaled adenosine?
Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like...
Gespeichert in:
Veröffentlicht in: | Life sciences (1973) 2001-08, Vol.69 (11), p.1225-1240 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1240 |
---|---|
container_issue | 11 |
container_start_page | 1225 |
container_title | Life sciences (1973) |
container_volume | 69 |
creator | Meade, Christopher J. Dumont, Indepencia Worrall, Liam |
description | Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like cells and mediators such as histamine, serotonin and lipoxygenase products. There is a strong link between responsiveness to adenosine and eosinophilia. In different animal models A
1, A
2b and A
3 adenosine receptor subclasses have all been implicated in inducing bronchospasm, whilst occupation of the A
2a receptor generally has no, or the opposite effect. At least two different mechanisms, both involving neural pathways, exist. One, involving the adenosine A
1 receptor, functions in mast cell depleted animals; the other requires interaction with a population of mast-like cells activated over A
2b or A
3 receptors. Not only histamine but also serotonin and lipoxygenase products released from the mast-like cells are potential mediators. In animal models good reactivity to adenosine receptor agonists is generally only found when the animals are first sensitized and exposed to allergen in ways likely to induce an allergic inflammation. An exception is the BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even without allergen exposure. This rat strain does however show evidence of spontaneous eosinophilic inflammation in the lung even without immunization. As mast cells both release adenosine and respond to adenosine, adenosine provides a non-specific method of amplifying specific signals resulting from IgE / antigen interaction. This mechanism may not only have a pathological significance in asthma; it may be part of a normal bodily defense response that in asthmatic subjects is inappropriately activated. |
doi_str_mv | 10.1016/S0024-3205(01)01231-0 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71147501</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0024320501012310</els_id><sourcerecordid>71147501</sourcerecordid><originalsourceid>FETCH-LOGICAL-c427t-85e9937d1a55430c5c187aeff1b92216c83a879781c685cd00a8d4e0d6cfa65f3</originalsourceid><addsrcrecordid>eNqFkMtOwzAQRS0EoqXwCSCvECwCM0kcp6sKVbykSiwAsbRce0JdpXGxU6T-PelDsGQ1mzNz7xzGzhFuELC4fQVI8yRLQVwBXgOmGSZwwPpYymECRYaHrP-L9NhJjHMAEEJmx6yHKFKUueyz8cdsza3nOrazhW6d4XE1nZNpIw8Ul76xPHoe2-Cbz3rNW89dM9M1Wa4tNT66hkan7KjSdaSz_Ryw94f7t_FTMnl5fB7fTRKTp7JNSkHDYSYtaiHyDIwwXVdNVYXTYZpiYcpMd-VliaYohbEAurQ5gS1MpQtRZQN2ubu7DP5rRbFVCxcN1bVuyK-ikoi5FIAdKHagCT7GQJVaBrfQYa0Q1Mae2tpTGzUKUG3tKej2LvYBq-mC7N_WXlcHjHYAdW9-OwoqGkeNIetC50xZ7_6J-AFhJH4Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71147501</pqid></control><display><type>article</type><title>Why do asthmatic subjects respond so strongly to inhaled adenosine?</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Meade, Christopher J. ; Dumont, Indepencia ; Worrall, Liam</creator><creatorcontrib>Meade, Christopher J. ; Dumont, Indepencia ; Worrall, Liam</creatorcontrib><description>Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like cells and mediators such as histamine, serotonin and lipoxygenase products. There is a strong link between responsiveness to adenosine and eosinophilia. In different animal models A
1, A
2b and A
3 adenosine receptor subclasses have all been implicated in inducing bronchospasm, whilst occupation of the A
2a receptor generally has no, or the opposite effect. At least two different mechanisms, both involving neural pathways, exist. One, involving the adenosine A
1 receptor, functions in mast cell depleted animals; the other requires interaction with a population of mast-like cells activated over A
2b or A
3 receptors. Not only histamine but also serotonin and lipoxygenase products released from the mast-like cells are potential mediators. In animal models good reactivity to adenosine receptor agonists is generally only found when the animals are first sensitized and exposed to allergen in ways likely to induce an allergic inflammation. An exception is the BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even without allergen exposure. This rat strain does however show evidence of spontaneous eosinophilic inflammation in the lung even without immunization. As mast cells both release adenosine and respond to adenosine, adenosine provides a non-specific method of amplifying specific signals resulting from IgE / antigen interaction. This mechanism may not only have a pathological significance in asthma; it may be part of a normal bodily defense response that in asthmatic subjects is inappropriately activated.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/S0024-3205(01)01231-0</identifier><identifier>PMID: 11521747</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Adenosine ; Adenosine-5'-(N-ethylcarboxamide) - administration & dosage ; Administration, Inhalation ; Animals ; Asthma ; Asthma - physiopathology ; Bronchial Spasm - physiopathology ; Bronchoconstriction - drug effects ; Bronchoconstriction - physiology ; Disease Models, Animal ; Eosinophil ; Eosinophilia - physiopathology ; Humans ; Hyperreactivity ; In Vitro Techniques ; Mast Cells - physiology ; Rats ; Rats, Inbred Strains ; Receptors, Purinergic P1 - classification ; Receptors, Purinergic P1 - physiology ; Vasodilator Agents - administration & dosage</subject><ispartof>Life sciences (1973), 2001-08, Vol.69 (11), p.1225-1240</ispartof><rights>2001 Elsevier Science Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-85e9937d1a55430c5c187aeff1b92216c83a879781c685cd00a8d4e0d6cfa65f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0024-3205(01)01231-0$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11521747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meade, Christopher J.</creatorcontrib><creatorcontrib>Dumont, Indepencia</creatorcontrib><creatorcontrib>Worrall, Liam</creatorcontrib><title>Why do asthmatic subjects respond so strongly to inhaled adenosine?</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like cells and mediators such as histamine, serotonin and lipoxygenase products. There is a strong link between responsiveness to adenosine and eosinophilia. In different animal models A
1, A
2b and A
3 adenosine receptor subclasses have all been implicated in inducing bronchospasm, whilst occupation of the A
2a receptor generally has no, or the opposite effect. At least two different mechanisms, both involving neural pathways, exist. One, involving the adenosine A
1 receptor, functions in mast cell depleted animals; the other requires interaction with a population of mast-like cells activated over A
2b or A
3 receptors. Not only histamine but also serotonin and lipoxygenase products released from the mast-like cells are potential mediators. In animal models good reactivity to adenosine receptor agonists is generally only found when the animals are first sensitized and exposed to allergen in ways likely to induce an allergic inflammation. An exception is the BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even without allergen exposure. This rat strain does however show evidence of spontaneous eosinophilic inflammation in the lung even without immunization. As mast cells both release adenosine and respond to adenosine, adenosine provides a non-specific method of amplifying specific signals resulting from IgE / antigen interaction. This mechanism may not only have a pathological significance in asthma; it may be part of a normal bodily defense response that in asthmatic subjects is inappropriately activated.</description><subject>Adenosine</subject><subject>Adenosine-5'-(N-ethylcarboxamide) - administration & dosage</subject><subject>Administration, Inhalation</subject><subject>Animals</subject><subject>Asthma</subject><subject>Asthma - physiopathology</subject><subject>Bronchial Spasm - physiopathology</subject><subject>Bronchoconstriction - drug effects</subject><subject>Bronchoconstriction - physiology</subject><subject>Disease Models, Animal</subject><subject>Eosinophil</subject><subject>Eosinophilia - physiopathology</subject><subject>Humans</subject><subject>Hyperreactivity</subject><subject>In Vitro Techniques</subject><subject>Mast Cells - physiology</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Receptors, Purinergic P1 - classification</subject><subject>Receptors, Purinergic P1 - physiology</subject><subject>Vasodilator Agents - administration & dosage</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtOwzAQRS0EoqXwCSCvECwCM0kcp6sKVbykSiwAsbRce0JdpXGxU6T-PelDsGQ1mzNz7xzGzhFuELC4fQVI8yRLQVwBXgOmGSZwwPpYymECRYaHrP-L9NhJjHMAEEJmx6yHKFKUueyz8cdsza3nOrazhW6d4XE1nZNpIw8Ul76xPHoe2-Cbz3rNW89dM9M1Wa4tNT66hkan7KjSdaSz_Ryw94f7t_FTMnl5fB7fTRKTp7JNSkHDYSYtaiHyDIwwXVdNVYXTYZpiYcpMd-VliaYohbEAurQ5gS1MpQtRZQN2ubu7DP5rRbFVCxcN1bVuyK-ikoi5FIAdKHagCT7GQJVaBrfQYa0Q1Mae2tpTGzUKUG3tKej2LvYBq-mC7N_WXlcHjHYAdW9-OwoqGkeNIetC50xZ7_6J-AFhJH4Q</recordid><startdate>20010803</startdate><enddate>20010803</enddate><creator>Meade, Christopher J.</creator><creator>Dumont, Indepencia</creator><creator>Worrall, Liam</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>20010803</creationdate><title>Why do asthmatic subjects respond so strongly to inhaled adenosine?</title><author>Meade, Christopher J. ; Dumont, Indepencia ; Worrall, Liam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-85e9937d1a55430c5c187aeff1b92216c83a879781c685cd00a8d4e0d6cfa65f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adenosine</topic><topic>Adenosine-5'-(N-ethylcarboxamide) - administration & dosage</topic><topic>Administration, Inhalation</topic><topic>Animals</topic><topic>Asthma</topic><topic>Asthma - physiopathology</topic><topic>Bronchial Spasm - physiopathology</topic><topic>Bronchoconstriction - drug effects</topic><topic>Bronchoconstriction - physiology</topic><topic>Disease Models, Animal</topic><topic>Eosinophil</topic><topic>Eosinophilia - physiopathology</topic><topic>Humans</topic><topic>Hyperreactivity</topic><topic>In Vitro Techniques</topic><topic>Mast Cells - physiology</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Receptors, Purinergic P1 - classification</topic><topic>Receptors, Purinergic P1 - physiology</topic><topic>Vasodilator Agents - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meade, Christopher J.</creatorcontrib><creatorcontrib>Dumont, Indepencia</creatorcontrib><creatorcontrib>Worrall, Liam</creatorcontrib><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>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meade, Christopher J.</au><au>Dumont, Indepencia</au><au>Worrall, Liam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Why do asthmatic subjects respond so strongly to inhaled adenosine?</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2001-08-03</date><risdate>2001</risdate><volume>69</volume><issue>11</issue><spage>1225</spage><epage>1240</epage><pages>1225-1240</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like cells and mediators such as histamine, serotonin and lipoxygenase products. There is a strong link between responsiveness to adenosine and eosinophilia. In different animal models A
1, A
2b and A
3 adenosine receptor subclasses have all been implicated in inducing bronchospasm, whilst occupation of the A
2a receptor generally has no, or the opposite effect. At least two different mechanisms, both involving neural pathways, exist. One, involving the adenosine A
1 receptor, functions in mast cell depleted animals; the other requires interaction with a population of mast-like cells activated over A
2b or A
3 receptors. Not only histamine but also serotonin and lipoxygenase products released from the mast-like cells are potential mediators. In animal models good reactivity to adenosine receptor agonists is generally only found when the animals are first sensitized and exposed to allergen in ways likely to induce an allergic inflammation. An exception is the BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even without allergen exposure. This rat strain does however show evidence of spontaneous eosinophilic inflammation in the lung even without immunization. As mast cells both release adenosine and respond to adenosine, adenosine provides a non-specific method of amplifying specific signals resulting from IgE / antigen interaction. This mechanism may not only have a pathological significance in asthma; it may be part of a normal bodily defense response that in asthmatic subjects is inappropriately activated.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>11521747</pmid><doi>10.1016/S0024-3205(01)01231-0</doi><tpages>16</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0024-3205 |
ispartof | Life sciences (1973), 2001-08, Vol.69 (11), p.1225-1240 |
issn | 0024-3205 1879-0631 |
language | eng |
recordid | cdi_proquest_miscellaneous_71147501 |
source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
subjects | Adenosine Adenosine-5'-(N-ethylcarboxamide) - administration & dosage Administration, Inhalation Animals Asthma Asthma - physiopathology Bronchial Spasm - physiopathology Bronchoconstriction - drug effects Bronchoconstriction - physiology Disease Models, Animal Eosinophil Eosinophilia - physiopathology Humans Hyperreactivity In Vitro Techniques Mast Cells - physiology Rats Rats, Inbred Strains Receptors, Purinergic P1 - classification Receptors, Purinergic P1 - physiology Vasodilator Agents - administration & dosage |
title | Why do asthmatic subjects respond so strongly to inhaled adenosine? |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T16%3A59%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Why%20do%20asthmatic%20subjects%20respond%20so%20strongly%20to%20inhaled%20adenosine?&rft.jtitle=Life%20sciences%20(1973)&rft.au=Meade,%20Christopher%20J.&rft.date=2001-08-03&rft.volume=69&rft.issue=11&rft.spage=1225&rft.epage=1240&rft.pages=1225-1240&rft.issn=0024-3205&rft.eissn=1879-0631&rft_id=info:doi/10.1016/S0024-3205(01)01231-0&rft_dat=%3Cproquest_cross%3E71147501%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=71147501&rft_id=info:pmid/11521747&rft_els_id=S0024320501012310&rfr_iscdi=true |