Characterization of the effects of cannabinoids on guinea‐pig tracheal smooth muscle tone: role in the modulation of acetylcholine release from parasympathetic nerves
We investigated the ability of the cannabinoid agonists CP55,940 (CB1/CB2) and anandamide (endogenous cannabinoid) to modulate electrical field stimulation (EFS)‐induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea‐pig trachea. We assessed whether modulation of...
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| creator | Spicuzza, Lucia Haddad, El‐Bdaoui Birrell, Mark Ling, Andrea Clarke, Deborah Venkatesan, Priya Barnes, Peter J Belvisi, Maria G |
| description | We investigated the ability of the cannabinoid agonists CP55,940 (CB1/CB2) and anandamide (endogenous cannabinoid) to modulate electrical field stimulation (EFS)‐induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea‐pig trachea. We assessed whether modulation of transmitter release translated to an impact on functional responses by investigating the effect of these agents on contractile responses evoked by EFS and ACh. Furthermore, we evaluated the ability of these compounds to elicit bronchodilation in pre‐contracted guinea‐pig tracheal strips.
CP55,940 and anandamide significantly inhibited EFS‐evoked ACh release (maximal inhibition of 35.1±2.9% and 33.4±6.4% at 1 μM, P |
| doi_str_mv | 10.1038/sj.bjp.0703497 |
| format | Article |
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CP55,940 and anandamide significantly inhibited EFS‐evoked ACh release (maximal inhibition of 35.1±2.9% and 33.4±6.4% at 1 μM, P<0.05, respectively). The CB1 receptor antagonist SR 141716A (1 μM), had no effect on ACh release and failed to reverse the inhibitory effect of CP55,940 (1 μM).
Paradoxically, CP55,940 had no significant effect on EFS‐evoked cholinergic contractile responses. Furthermore, CP55,940 did not relax pre‐contracted tracheal strips or affect contractile responses to exogenous ACh. This lack of activity on smooth muscle tone is consistent with the fact that no detectable specific binding of [3H] CP55,940 was found in tracheal homogenates.
These data suggest that cannabinoid agonists inhibit ACh release from cholinergic nerve terminals via activation of CB2 receptors but that this inhibitory action does not impact on functional responses such as cholinergic contraction.
British Journal of Pharmacology (2000) 130, 1720–1726; doi:10.1038/sj.bjp.0703497</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0703497</identifier><identifier>PMID: 10928980</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Acetylcholine - metabolism ; acetylcholine release ; airways ; Analgesics - pharmacology ; Analgesics, Non-Narcotic - pharmacology ; anandamine ; Animals ; Arachidonic Acids - pharmacology ; Binding, Competitive ; Biological and medical sciences ; Cannabinoid ; Cannabinoids - pharmacology ; Carbachol - pharmacology ; contraction ; Cyclohexanols - pharmacology ; Electric Stimulation ; Endocannabinoids ; Guinea Pigs ; In Vitro Techniques ; Male ; Medical sciences ; Muscle Contraction - drug effects ; Muscle, Smooth - drug effects ; Muscle, Smooth - physiology ; neurotransmission ; Parasympathetic Nervous System - drug effects ; Parasympathetic Nervous System - metabolism ; Parasympatholytics - pharmacology ; Pharmacology. Drug treatments ; Polyunsaturated Alkamides ; Respiratory system ; trachea ; Trachea - cytology ; Trachea - drug effects ; Trachea - metabolism ; Tritium</subject><ispartof>British journal of pharmacology, 2000-08, Vol.130 (7), p.1720-1726</ispartof><rights>2000 British Pharmacological Society</rights><rights>2000 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Aug 2000</rights><rights>Copyright 2000, Nature Publishing Group 2000 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5178-2506c111204043ff5caadcdef0ee9d9b70701754c87e90dd90be61d5a15aa2ab3</citedby><cites>FETCH-LOGICAL-c5178-2506c111204043ff5caadcdef0ee9d9b70701754c87e90dd90be61d5a15aa2ab3</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/PMC1572241/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1572241/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1447537$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10928980$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spicuzza, Lucia</creatorcontrib><creatorcontrib>Haddad, El‐Bdaoui</creatorcontrib><creatorcontrib>Birrell, Mark</creatorcontrib><creatorcontrib>Ling, Andrea</creatorcontrib><creatorcontrib>Clarke, Deborah</creatorcontrib><creatorcontrib>Venkatesan, Priya</creatorcontrib><creatorcontrib>Barnes, Peter J</creatorcontrib><creatorcontrib>Belvisi, Maria G</creatorcontrib><title>Characterization of the effects of cannabinoids on guinea‐pig tracheal smooth muscle tone: role in the modulation of acetylcholine release from parasympathetic nerves</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>We investigated the ability of the cannabinoid agonists CP55,940 (CB1/CB2) and anandamide (endogenous cannabinoid) to modulate electrical field stimulation (EFS)‐induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea‐pig trachea. We assessed whether modulation of transmitter release translated to an impact on functional responses by investigating the effect of these agents on contractile responses evoked by EFS and ACh. Furthermore, we evaluated the ability of these compounds to elicit bronchodilation in pre‐contracted guinea‐pig tracheal strips.
CP55,940 and anandamide significantly inhibited EFS‐evoked ACh release (maximal inhibition of 35.1±2.9% and 33.4±6.4% at 1 μM, P<0.05, respectively). The CB1 receptor antagonist SR 141716A (1 μM), had no effect on ACh release and failed to reverse the inhibitory effect of CP55,940 (1 μM).
Paradoxically, CP55,940 had no significant effect on EFS‐evoked cholinergic contractile responses. Furthermore, CP55,940 did not relax pre‐contracted tracheal strips or affect contractile responses to exogenous ACh. This lack of activity on smooth muscle tone is consistent with the fact that no detectable specific binding of [3H] CP55,940 was found in tracheal homogenates.
These data suggest that cannabinoid agonists inhibit ACh release from cholinergic nerve terminals via activation of CB2 receptors but that this inhibitory action does not impact on functional responses such as cholinergic contraction.
British Journal of Pharmacology (2000) 130, 1720–1726; doi:10.1038/sj.bjp.0703497</description><subject>Acetylcholine - metabolism</subject><subject>acetylcholine release</subject><subject>airways</subject><subject>Analgesics - pharmacology</subject><subject>Analgesics, Non-Narcotic - pharmacology</subject><subject>anandamine</subject><subject>Animals</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Cannabinoid</subject><subject>Cannabinoids - pharmacology</subject><subject>Carbachol - pharmacology</subject><subject>contraction</subject><subject>Cyclohexanols - pharmacology</subject><subject>Electric Stimulation</subject><subject>Endocannabinoids</subject><subject>Guinea Pigs</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle, Smooth - drug effects</subject><subject>Muscle, Smooth - physiology</subject><subject>neurotransmission</subject><subject>Parasympathetic Nervous System - drug effects</subject><subject>Parasympathetic Nervous System - metabolism</subject><subject>Parasympatholytics - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyunsaturated Alkamides</subject><subject>Respiratory system</subject><subject>trachea</subject><subject>Trachea - cytology</subject><subject>Trachea - drug effects</subject><subject>Trachea - metabolism</subject><subject>Tritium</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFksGO0zAQhi0EYkvhyhFZCHFLsZO4TjisBBWwSCvBAc7WxJk0rhw72MmicuIReAyeiyfBpdWycNmTbc03_8z8HkIec7birKhexN2q2Y0rJllR1vIOWfBSrjNRVPwuWTDGZMZ5VZ2RBzHuGEtBKe6TM87qvKortiA_Nz0E0BMG8w0m4x31HZ16pNh1qKd4eGpwDhrjvGnT29HtbBzCr-8_RrOlU8ruESyNg_dTT4c5aot08g5f0uDT1bg_goNvZ3tdAjROe6t7b5MWDWgRItIu-IGOqaG4H0ZIWZPR1GG4wviQ3OvARnx0Opfk89s3nzYX2eWHd-83ry4zLbisslywteac56xkZdF1QgO0usWOIdZt3cjkFJei1JXEmrVtzRpc81YAFwA5NMWSnB91x7kZsNXo0oRWjcEMEPbKg1H_Rpzp1dZfKS5knpc8CTw_CQT_ZcY4qcFEjdaCQz9HJXmyviyrW0Eu17zO08cuydP_wJ2fg0suqJxLXpU1EwlaHSEdfIwBu-uWOVOHVVFxp9KqqNOqpIQnNwe9gR93IwHPTgBEDbYL4LSJf7mylKI46BRH7KuxuL-lqnr98SIZVRW_AZKe3g8</recordid><startdate>200008</startdate><enddate>200008</enddate><creator>Spicuzza, Lucia</creator><creator>Haddad, El‐Bdaoui</creator><creator>Birrell, Mark</creator><creator>Ling, Andrea</creator><creator>Clarke, Deborah</creator><creator>Venkatesan, Priya</creator><creator>Barnes, Peter J</creator><creator>Belvisi, Maria G</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200008</creationdate><title>Characterization of the effects of cannabinoids on guinea‐pig tracheal smooth muscle tone: role in the modulation of acetylcholine release from parasympathetic nerves</title><author>Spicuzza, Lucia ; Haddad, El‐Bdaoui ; Birrell, Mark ; Ling, Andrea ; Clarke, Deborah ; Venkatesan, Priya ; Barnes, Peter J ; Belvisi, Maria G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5178-2506c111204043ff5caadcdef0ee9d9b70701754c87e90dd90be61d5a15aa2ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Acetylcholine - metabolism</topic><topic>acetylcholine release</topic><topic>airways</topic><topic>Analgesics - pharmacology</topic><topic>Analgesics, Non-Narcotic - pharmacology</topic><topic>anandamine</topic><topic>Animals</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Cannabinoid</topic><topic>Cannabinoids - pharmacology</topic><topic>Carbachol - pharmacology</topic><topic>contraction</topic><topic>Cyclohexanols - pharmacology</topic><topic>Electric Stimulation</topic><topic>Endocannabinoids</topic><topic>Guinea Pigs</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle, Smooth - drug effects</topic><topic>Muscle, Smooth - physiology</topic><topic>neurotransmission</topic><topic>Parasympathetic Nervous System - drug effects</topic><topic>Parasympathetic Nervous System - metabolism</topic><topic>Parasympatholytics - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyunsaturated Alkamides</topic><topic>Respiratory system</topic><topic>trachea</topic><topic>Trachea - cytology</topic><topic>Trachea - drug effects</topic><topic>Trachea - metabolism</topic><topic>Tritium</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spicuzza, Lucia</creatorcontrib><creatorcontrib>Haddad, El‐Bdaoui</creatorcontrib><creatorcontrib>Birrell, Mark</creatorcontrib><creatorcontrib>Ling, Andrea</creatorcontrib><creatorcontrib>Clarke, Deborah</creatorcontrib><creatorcontrib>Venkatesan, Priya</creatorcontrib><creatorcontrib>Barnes, Peter J</creatorcontrib><creatorcontrib>Belvisi, Maria G</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>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Spicuzza, Lucia</au><au>Haddad, El‐Bdaoui</au><au>Birrell, Mark</au><au>Ling, Andrea</au><au>Clarke, Deborah</au><au>Venkatesan, Priya</au><au>Barnes, Peter J</au><au>Belvisi, Maria G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of the effects of cannabinoids on guinea‐pig tracheal smooth muscle tone: role in the modulation of acetylcholine release from parasympathetic nerves</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2000-08</date><risdate>2000</risdate><volume>130</volume><issue>7</issue><spage>1720</spage><epage>1726</epage><pages>1720-1726</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>We investigated the ability of the cannabinoid agonists CP55,940 (CB1/CB2) and anandamide (endogenous cannabinoid) to modulate electrical field stimulation (EFS)‐induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea‐pig trachea. We assessed whether modulation of transmitter release translated to an impact on functional responses by investigating the effect of these agents on contractile responses evoked by EFS and ACh. Furthermore, we evaluated the ability of these compounds to elicit bronchodilation in pre‐contracted guinea‐pig tracheal strips.
CP55,940 and anandamide significantly inhibited EFS‐evoked ACh release (maximal inhibition of 35.1±2.9% and 33.4±6.4% at 1 μM, P<0.05, respectively). The CB1 receptor antagonist SR 141716A (1 μM), had no effect on ACh release and failed to reverse the inhibitory effect of CP55,940 (1 μM).
Paradoxically, CP55,940 had no significant effect on EFS‐evoked cholinergic contractile responses. Furthermore, CP55,940 did not relax pre‐contracted tracheal strips or affect contractile responses to exogenous ACh. This lack of activity on smooth muscle tone is consistent with the fact that no detectable specific binding of [3H] CP55,940 was found in tracheal homogenates.
These data suggest that cannabinoid agonists inhibit ACh release from cholinergic nerve terminals via activation of CB2 receptors but that this inhibitory action does not impact on functional responses such as cholinergic contraction.
British Journal of Pharmacology (2000) 130, 1720–1726; doi:10.1038/sj.bjp.0703497</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>10928980</pmid><doi>10.1038/sj.bjp.0703497</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylcholine - metabolism acetylcholine release airways Analgesics - pharmacology Analgesics, Non-Narcotic - pharmacology anandamine Animals Arachidonic Acids - pharmacology Binding, Competitive Biological and medical sciences Cannabinoid Cannabinoids - pharmacology Carbachol - pharmacology contraction Cyclohexanols - pharmacology Electric Stimulation Endocannabinoids Guinea Pigs In Vitro Techniques Male Medical sciences Muscle Contraction - drug effects Muscle, Smooth - drug effects Muscle, Smooth - physiology neurotransmission Parasympathetic Nervous System - drug effects Parasympathetic Nervous System - metabolism Parasympatholytics - pharmacology Pharmacology. Drug treatments Polyunsaturated Alkamides Respiratory system trachea Trachea - cytology Trachea - drug effects Trachea - metabolism Tritium |
| title | Characterization of the effects of cannabinoids on guinea‐pig tracheal smooth muscle tone: role in the modulation of acetylcholine release from parasympathetic nerves |
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