Cannabinoid receptor agonists inhibit depolarization‐induced calcium influx in cerebellar granule neurons
Neuronal cannabinoid receptors (CB1) are coupled to inhibition of voltage‐sensitive Ca2+ channels (VSCCs) in several cell types. The purpose of these studies was to characterize the interaction between endogenous CB1 receptors and VSCCs in cerebellar granule neurons (CGN). Ca2+ transients were evoke...
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| Veröffentlicht in: | Journal of neurochemistry 2001-10, Vol.79 (2), p.371-381 |
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| creator | Nogueron, M. Isabel Porgilsson, Bjorn Schneider, Wendy E. Stucky, Cheryl L. Hillard, Cecilia J. |
| description | Neuronal cannabinoid receptors (CB1) are coupled to inhibition of voltage‐sensitive Ca2+ channels (VSCCs) in several cell types. The purpose of these studies was to characterize the interaction between endogenous CB1 receptors and VSCCs in cerebellar granule neurons (CGN). Ca2+ transients were evoked by KCl‐induced depolarization and imaged using fura‐2. The CB1 receptor agonists CP55940, Win 55212–2 and N‐arachidonylethanolamine (anandamide) produced concentration‐related decreases in peak amplitude of the Ca2+ response and total Ca2+ influx. Pre‐treatment of CGN with pertussis toxin abolished agonist‐mediated inhibition. The inhibitory effect of Win 55212–2 on Ca2+ influx was additive with inhibition produced by ω‐agatoxin IVA and nifedipine but not with ω‐conotoxin GVIA, indicating that N‐type VSCCs are the primary effector. Paradoxically, the CB1 receptor antagonist, SR141716, also inhibited KCl‐induced Ca2+ influx into CGN in a concentration‐related manner. SR141716 inhibition was pertussis toxin‐insensitive and was not additive with the inhibition produced by Win 55212–2. Confocal imaging of CGN in primary culture demonstrate a high density of CB1 receptor expression on CGN plasma membranes, including the neuritic processes. These data demonstrate that the CB1 receptor is highly expressed by CGN and agonists serve as potent and efficacious inhibitory modulators of Ca2+ influx through N‐type VSCC. |
| doi_str_mv | 10.1046/j.1471-4159.2001.00567.x |
| format | Article |
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Isabel ; Porgilsson, Bjorn ; Schneider, Wendy E. ; Stucky, Cheryl L. ; Hillard, Cecilia J.</creator><creatorcontrib>Nogueron, M. Isabel ; Porgilsson, Bjorn ; Schneider, Wendy E. ; Stucky, Cheryl L. ; Hillard, Cecilia J.</creatorcontrib><description>Neuronal cannabinoid receptors (CB1) are coupled to inhibition of voltage‐sensitive Ca2+ channels (VSCCs) in several cell types. The purpose of these studies was to characterize the interaction between endogenous CB1 receptors and VSCCs in cerebellar granule neurons (CGN). Ca2+ transients were evoked by KCl‐induced depolarization and imaged using fura‐2. The CB1 receptor agonists CP55940, Win 55212–2 and N‐arachidonylethanolamine (anandamide) produced concentration‐related decreases in peak amplitude of the Ca2+ response and total Ca2+ influx. Pre‐treatment of CGN with pertussis toxin abolished agonist‐mediated inhibition. The inhibitory effect of Win 55212–2 on Ca2+ influx was additive with inhibition produced by ω‐agatoxin IVA and nifedipine but not with ω‐conotoxin GVIA, indicating that N‐type VSCCs are the primary effector. Paradoxically, the CB1 receptor antagonist, SR141716, also inhibited KCl‐induced Ca2+ influx into CGN in a concentration‐related manner. SR141716 inhibition was pertussis toxin‐insensitive and was not additive with the inhibition produced by Win 55212–2. Confocal imaging of CGN in primary culture demonstrate a high density of CB1 receptor expression on CGN plasma membranes, including the neuritic processes. These data demonstrate that the CB1 receptor is highly expressed by CGN and agonists serve as potent and efficacious inhibitory modulators of Ca2+ influx through N‐type VSCC.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1046/j.1471-4159.2001.00567.x</identifier><identifier>PMID: 11677265</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>anandamide ; Animals ; Arachidonic Acids - pharmacology ; Benzoxazines ; Biological and medical sciences ; Calcium - metabolism ; Calcium Channel Blockers - pharmacology ; Calcium Channels - physiology ; Cells, Cultured ; Central nervous system ; Central neurotransmission. Neuromudulation. Pathways and receptors ; Cerebellum - cytology ; Cerebellum - metabolism ; Cerebellum - physiology ; confocal imaging ; Electrophysiology ; Endocannabinoids ; Female ; Fundamental and applied biological sciences. Psychology ; fura‐2 ; Male ; Morpholines - pharmacology ; Naphthalenes - pharmacology ; Neurons - metabolism ; Neurons - physiology ; Polyunsaturated Alkamides ; Rats ; Receptors, Cannabinoid ; Receptors, Drug - agonists ; Receptors, Drug - antagonists & inhibitors ; Receptors, Drug - physiology ; Vertebrates: nervous system and sense organs ; voltage‐sensitive calcium channels ; ω‐conotoxin GVIA</subject><ispartof>Journal of neurochemistry, 2001-10, Vol.79 (2), p.371-381</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4757-ea2819eb04a852419a5ddbfbea934144c2936882edd5ef9d2c4cc2d6d184aea23</citedby><cites>FETCH-LOGICAL-c4757-ea2819eb04a852419a5ddbfbea934144c2936882edd5ef9d2c4cc2d6d184aea23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1471-4159.2001.00567.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1471-4159.2001.00567.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14150591$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11677265$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nogueron, M. Isabel</creatorcontrib><creatorcontrib>Porgilsson, Bjorn</creatorcontrib><creatorcontrib>Schneider, Wendy E.</creatorcontrib><creatorcontrib>Stucky, Cheryl L.</creatorcontrib><creatorcontrib>Hillard, Cecilia J.</creatorcontrib><title>Cannabinoid receptor agonists inhibit depolarization‐induced calcium influx in cerebellar granule neurons</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>Neuronal cannabinoid receptors (CB1) are coupled to inhibition of voltage‐sensitive Ca2+ channels (VSCCs) in several cell types. The purpose of these studies was to characterize the interaction between endogenous CB1 receptors and VSCCs in cerebellar granule neurons (CGN). Ca2+ transients were evoked by KCl‐induced depolarization and imaged using fura‐2. The CB1 receptor agonists CP55940, Win 55212–2 and N‐arachidonylethanolamine (anandamide) produced concentration‐related decreases in peak amplitude of the Ca2+ response and total Ca2+ influx. Pre‐treatment of CGN with pertussis toxin abolished agonist‐mediated inhibition. The inhibitory effect of Win 55212–2 on Ca2+ influx was additive with inhibition produced by ω‐agatoxin IVA and nifedipine but not with ω‐conotoxin GVIA, indicating that N‐type VSCCs are the primary effector. Paradoxically, the CB1 receptor antagonist, SR141716, also inhibited KCl‐induced Ca2+ influx into CGN in a concentration‐related manner. SR141716 inhibition was pertussis toxin‐insensitive and was not additive with the inhibition produced by Win 55212–2. Confocal imaging of CGN in primary culture demonstrate a high density of CB1 receptor expression on CGN plasma membranes, including the neuritic processes. These data demonstrate that the CB1 receptor is highly expressed by CGN and agonists serve as potent and efficacious inhibitory modulators of Ca2+ influx through N‐type VSCC.</description><subject>anandamide</subject><subject>Animals</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Benzoxazines</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channels - physiology</subject><subject>Cells, Cultured</subject><subject>Central nervous system</subject><subject>Central neurotransmission. Neuromudulation. Pathways and receptors</subject><subject>Cerebellum - cytology</subject><subject>Cerebellum - metabolism</subject><subject>Cerebellum - physiology</subject><subject>confocal imaging</subject><subject>Electrophysiology</subject><subject>Endocannabinoids</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>fura‐2</subject><subject>Male</subject><subject>Morpholines - pharmacology</subject><subject>Naphthalenes - pharmacology</subject><subject>Neurons - metabolism</subject><subject>Neurons - physiology</subject><subject>Polyunsaturated Alkamides</subject><subject>Rats</subject><subject>Receptors, Cannabinoid</subject><subject>Receptors, Drug - agonists</subject><subject>Receptors, Drug - antagonists & inhibitors</subject><subject>Receptors, Drug - physiology</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>voltage‐sensitive calcium channels</subject><subject>ω‐conotoxin GVIA</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU2O1DAQhS0EYpqBKyBvYJfgchzHkdigFr8awQbWlmNXBjdpu7ET0cOKI3BGToJDt5glrKqk-l5V6T1CKLAamJDPdjWIDioBbV9zxqBmrJVdfbxDNn8Hd8mGMc6rhgl-QR7kvCugFBLukwsA2XVcthvyZWtCMIMP0Tua0OJhjoma6xh8njP14bMf_EwdHuJkkv9uZh_Drx8_fXCLRUetmaxf9gUcp-VYCrWYcMCp0PQ6mbBMSAMuKYb8kNwbzZTx0blekk-vXn7cvqmuPrx-u31xVVnRtV2FhivocWDCqJYL6E3r3DAOaPpGgBCW941UiqNzLY6941ZYy510oIQp4uaSPD3tPaT4dcE8673Pdn0pYFyy7jhvgCnxTxAUZ6pXsoDqBNoUc0446kPye5NuNDC9JqJ3ejVer8brNRH9JxF9LNLH5xvLsEd3KzxHUIAnZ8Dk4uZYPLM-33JlJWt7KNzzE_fNT3jz3w_od--3pWl-A-A8qjQ</recordid><startdate>200110</startdate><enddate>200110</enddate><creator>Nogueron, M. Isabel</creator><creator>Porgilsson, Bjorn</creator><creator>Schneider, Wendy E.</creator><creator>Stucky, Cheryl L.</creator><creator>Hillard, Cecilia J.</creator><general>Blackwell Science Ltd</general><general>Blackwell</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>7QP</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>200110</creationdate><title>Cannabinoid receptor agonists inhibit depolarization‐induced calcium influx in cerebellar granule neurons</title><author>Nogueron, M. Isabel ; Porgilsson, Bjorn ; Schneider, Wendy E. ; Stucky, Cheryl L. ; Hillard, Cecilia J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4757-ea2819eb04a852419a5ddbfbea934144c2936882edd5ef9d2c4cc2d6d184aea23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>anandamide</topic><topic>Animals</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Benzoxazines</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channels - physiology</topic><topic>Cells, Cultured</topic><topic>Central nervous system</topic><topic>Central neurotransmission. Neuromudulation. Pathways and receptors</topic><topic>Cerebellum - cytology</topic><topic>Cerebellum - metabolism</topic><topic>Cerebellum - physiology</topic><topic>confocal imaging</topic><topic>Electrophysiology</topic><topic>Endocannabinoids</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>fura‐2</topic><topic>Male</topic><topic>Morpholines - pharmacology</topic><topic>Naphthalenes - pharmacology</topic><topic>Neurons - metabolism</topic><topic>Neurons - physiology</topic><topic>Polyunsaturated Alkamides</topic><topic>Rats</topic><topic>Receptors, Cannabinoid</topic><topic>Receptors, Drug - agonists</topic><topic>Receptors, Drug - antagonists & inhibitors</topic><topic>Receptors, Drug - physiology</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>voltage‐sensitive calcium channels</topic><topic>ω‐conotoxin GVIA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nogueron, M. Isabel</creatorcontrib><creatorcontrib>Porgilsson, Bjorn</creatorcontrib><creatorcontrib>Schneider, Wendy E.</creatorcontrib><creatorcontrib>Stucky, Cheryl L.</creatorcontrib><creatorcontrib>Hillard, Cecilia J.</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>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nogueron, M. Isabel</au><au>Porgilsson, Bjorn</au><au>Schneider, Wendy E.</au><au>Stucky, Cheryl L.</au><au>Hillard, Cecilia J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cannabinoid receptor agonists inhibit depolarization‐induced calcium influx in cerebellar granule neurons</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2001-10</date><risdate>2001</risdate><volume>79</volume><issue>2</issue><spage>371</spage><epage>381</epage><pages>371-381</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>Neuronal cannabinoid receptors (CB1) are coupled to inhibition of voltage‐sensitive Ca2+ channels (VSCCs) in several cell types. The purpose of these studies was to characterize the interaction between endogenous CB1 receptors and VSCCs in cerebellar granule neurons (CGN). Ca2+ transients were evoked by KCl‐induced depolarization and imaged using fura‐2. The CB1 receptor agonists CP55940, Win 55212–2 and N‐arachidonylethanolamine (anandamide) produced concentration‐related decreases in peak amplitude of the Ca2+ response and total Ca2+ influx. Pre‐treatment of CGN with pertussis toxin abolished agonist‐mediated inhibition. The inhibitory effect of Win 55212–2 on Ca2+ influx was additive with inhibition produced by ω‐agatoxin IVA and nifedipine but not with ω‐conotoxin GVIA, indicating that N‐type VSCCs are the primary effector. Paradoxically, the CB1 receptor antagonist, SR141716, also inhibited KCl‐induced Ca2+ influx into CGN in a concentration‐related manner. SR141716 inhibition was pertussis toxin‐insensitive and was not additive with the inhibition produced by Win 55212–2. Confocal imaging of CGN in primary culture demonstrate a high density of CB1 receptor expression on CGN plasma membranes, including the neuritic processes. These data demonstrate that the CB1 receptor is highly expressed by CGN and agonists serve as potent and efficacious inhibitory modulators of Ca2+ influx through N‐type VSCC.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>11677265</pmid><doi>10.1046/j.1471-4159.2001.00567.x</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | anandamide Animals Arachidonic Acids - pharmacology Benzoxazines Biological and medical sciences Calcium - metabolism Calcium Channel Blockers - pharmacology Calcium Channels - physiology Cells, Cultured Central nervous system Central neurotransmission. Neuromudulation. Pathways and receptors Cerebellum - cytology Cerebellum - metabolism Cerebellum - physiology confocal imaging Electrophysiology Endocannabinoids Female Fundamental and applied biological sciences. Psychology fura‐2 Male Morpholines - pharmacology Naphthalenes - pharmacology Neurons - metabolism Neurons - physiology Polyunsaturated Alkamides Rats Receptors, Cannabinoid Receptors, Drug - agonists Receptors, Drug - antagonists & inhibitors Receptors, Drug - physiology Vertebrates: nervous system and sense organs voltage‐sensitive calcium channels ω‐conotoxin GVIA |
| title | Cannabinoid receptor agonists inhibit depolarization‐induced calcium influx in cerebellar granule neurons |
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