Dantrolene inhibits NMDA-induced 45Ca uptake in cultured cerebellar granule neurons
Dantrolene is an inhibitor of a skeletal muscle subtype of ryanodine receptors that stabilizes intracellular calcium concentrations and exerts neuroprotective effects in neurons submitted to excitotoxic challenges. The mechanisms of dantrolene-induced neuroprotection are not clear. In this study, us...
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| Veröffentlicht in: | Neurochemistry international 2003-09, Vol.43 (4-5), p.273-278 |
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| creator | Makarewicz, Dorota Ziemińska, Elżbieta Łazarewicz, Jerzy W. |
| description | Dantrolene is an inhibitor of a skeletal muscle subtype of ryanodine receptors that stabilizes intracellular calcium concentrations and exerts neuroprotective effects in neurons submitted to excitotoxic challenges. The mechanisms of dantrolene-induced neuroprotection are not clear. In this study, using a model of cultured rat cerebellar granule neurons, we demonstrated that dantrolene inhibits NMDA-evoked 45Ca uptake, indicating that this drug may inhibit the activity of NMDA receptor channels. Primary neuronal cultures were incubated for 10min in Mg2+-free ionic medium with NMDA and 45Ca in the presence of different concentrations of dantrolene, then radioactivity in neurons was measured by liquid scintillation spectroscopy. The results demonstrated that dantrolene, applied at micromolar concentrations, inhibits NMDA-evoked 45Ca uptake in neurons in a dose-dependent manner. DMSO, a vehicle to dantrolene, in concentrations used in this study had no effect on NMDA-evoked 45Ca uptake. These results, indicating that dantrolene inhibits activation of the NMDA receptors, might at least partially explain the mechanisms of a dantrolene-evoked protection of neurons against excitotoxicity mediated by agonists of NMDA receptors. |
| doi_str_mv | 10.1016/S0197-0186(03)00012-3 |
| format | Article |
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The mechanisms of dantrolene-induced neuroprotection are not clear. In this study, using a model of cultured rat cerebellar granule neurons, we demonstrated that dantrolene inhibits NMDA-evoked 45Ca uptake, indicating that this drug may inhibit the activity of NMDA receptor channels. Primary neuronal cultures were incubated for 10min in Mg2+-free ionic medium with NMDA and 45Ca in the presence of different concentrations of dantrolene, then radioactivity in neurons was measured by liquid scintillation spectroscopy. The results demonstrated that dantrolene, applied at micromolar concentrations, inhibits NMDA-evoked 45Ca uptake in neurons in a dose-dependent manner. DMSO, a vehicle to dantrolene, in concentrations used in this study had no effect on NMDA-evoked 45Ca uptake. These results, indicating that dantrolene inhibits activation of the NMDA receptors, might at least partially explain the mechanisms of a dantrolene-evoked protection of neurons against excitotoxicity mediated by agonists of NMDA receptors.</description><identifier>ISSN: 0197-0186</identifier><identifier>EISSN: 1872-9754</identifier><identifier>DOI: 10.1016/S0197-0186(03)00012-3</identifier><identifier>PMID: 12742069</identifier><identifier>CODEN: NEUIDS</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>[formula omitted] uptake ; Animals ; Biological and medical sciences ; Calcium - metabolism ; Cells, Cultured ; Cerebellar granule neurons ; Cerebellum - metabolism ; Cerebellum - physiology ; Cytoplasmic Granules - metabolism ; Cytoplasmic Granules - physiology ; Dantrolene ; Dantrolene - pharmacology ; DMSO ; Fundamental and applied biological sciences. Psychology ; N-Methylaspartate - antagonists & inhibitors ; N-Methylaspartate - physiology ; NMDA receptors ; Rats</subject><ispartof>Neurochemistry international, 2003-09, Vol.43 (4-5), p.273-278</ispartof><rights>2003 Elsevier Science Ltd</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2389-b58971e785de8d461778357fb41bc59d9ab62dbdc5aba2fc704462095d4604093</citedby><cites>FETCH-LOGICAL-c2389-b58971e785de8d461778357fb41bc59d9ab62dbdc5aba2fc704462095d4604093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0197-0186(03)00012-3$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>309,310,314,780,784,789,790,3550,23930,23931,25140,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14811051$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12742069$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Makarewicz, Dorota</creatorcontrib><creatorcontrib>Ziemińska, Elżbieta</creatorcontrib><creatorcontrib>Łazarewicz, Jerzy W.</creatorcontrib><title>Dantrolene inhibits NMDA-induced 45Ca uptake in cultured cerebellar granule neurons</title><title>Neurochemistry international</title><addtitle>Neurochem Int</addtitle><description>Dantrolene is an inhibitor of a skeletal muscle subtype of ryanodine receptors that stabilizes intracellular calcium concentrations and exerts neuroprotective effects in neurons submitted to excitotoxic challenges. The mechanisms of dantrolene-induced neuroprotection are not clear. In this study, using a model of cultured rat cerebellar granule neurons, we demonstrated that dantrolene inhibits NMDA-evoked 45Ca uptake, indicating that this drug may inhibit the activity of NMDA receptor channels. Primary neuronal cultures were incubated for 10min in Mg2+-free ionic medium with NMDA and 45Ca in the presence of different concentrations of dantrolene, then radioactivity in neurons was measured by liquid scintillation spectroscopy. The results demonstrated that dantrolene, applied at micromolar concentrations, inhibits NMDA-evoked 45Ca uptake in neurons in a dose-dependent manner. DMSO, a vehicle to dantrolene, in concentrations used in this study had no effect on NMDA-evoked 45Ca uptake. These results, indicating that dantrolene inhibits activation of the NMDA receptors, might at least partially explain the mechanisms of a dantrolene-evoked protection of neurons against excitotoxicity mediated by agonists of NMDA receptors.</description><subject>[formula omitted] uptake</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Cells, Cultured</subject><subject>Cerebellar granule neurons</subject><subject>Cerebellum - metabolism</subject><subject>Cerebellum - physiology</subject><subject>Cytoplasmic Granules - metabolism</subject><subject>Cytoplasmic Granules - physiology</subject><subject>Dantrolene</subject><subject>Dantrolene - pharmacology</subject><subject>DMSO</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>N-Methylaspartate - antagonists & inhibitors</subject><subject>N-Methylaspartate - physiology</subject><subject>NMDA receptors</subject><subject>Rats</subject><issn>0197-0186</issn><issn>1872-9754</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0MuKFDEUgOEgitOOPoJSG0UXpSe3SmUlQ483GHUxug65nNJodapNKoJvb3q6cZauAuE7yeEn5DGFlxTo8OoaqFY90HF4DvwFAFDW8ztkQ0fFeq2kuEs2_8gZeVDKj4aUBnmfnFGmBINBb8j1pU1rXmZM2MX0Pbq4lu7Tx8uLPqZQPYZOyK3t6n61Pw-i83Vea273HjM6nGebu2_Zpjpjl7DmJZWH5N5k54KPTuc5-fr2zZft-_7q87sP24ur3jM-6t7JUSuKapQBxyAGqtTIpZqcoM5LHbR1AwsueGmdZZNXIMTAQMtmQYDm5-TZ8d19Xn5VLKvZxeIPKyVcajGKM8VhhAblEfq8lJJxMvscdzb_MRTMoaa5qWkOqQxwc1PT8Db35PRBdTsMt1OnfA08PQFbvJ2n1sHHcuvESClI2tzro8OW43fEbIqPmFremNGvJizxP6v8BbeQj-s</recordid><startdate>200309</startdate><enddate>200309</enddate><creator>Makarewicz, Dorota</creator><creator>Ziemińska, Elżbieta</creator><creator>Łazarewicz, Jerzy W.</creator><general>Elsevier Ltd</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>200309</creationdate><title>Dantrolene inhibits NMDA-induced 45Ca uptake in cultured cerebellar granule neurons</title><author>Makarewicz, Dorota ; Ziemińska, Elżbieta ; Łazarewicz, Jerzy W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2389-b58971e785de8d461778357fb41bc59d9ab62dbdc5aba2fc704462095d4604093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>[formula omitted] uptake</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Cells, Cultured</topic><topic>Cerebellar granule neurons</topic><topic>Cerebellum - metabolism</topic><topic>Cerebellum - physiology</topic><topic>Cytoplasmic Granules - metabolism</topic><topic>Cytoplasmic Granules - physiology</topic><topic>Dantrolene</topic><topic>Dantrolene - pharmacology</topic><topic>DMSO</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>N-Methylaspartate - antagonists & inhibitors</topic><topic>N-Methylaspartate - physiology</topic><topic>NMDA receptors</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Makarewicz, Dorota</creatorcontrib><creatorcontrib>Ziemińska, Elżbieta</creatorcontrib><creatorcontrib>Łazarewicz, Jerzy W.</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>Neurochemistry international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Makarewicz, Dorota</au><au>Ziemińska, Elżbieta</au><au>Łazarewicz, Jerzy W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dantrolene inhibits NMDA-induced 45Ca uptake in cultured cerebellar granule neurons</atitle><jtitle>Neurochemistry international</jtitle><addtitle>Neurochem Int</addtitle><date>2003-09</date><risdate>2003</risdate><volume>43</volume><issue>4-5</issue><spage>273</spage><epage>278</epage><pages>273-278</pages><issn>0197-0186</issn><eissn>1872-9754</eissn><coden>NEUIDS</coden><abstract>Dantrolene is an inhibitor of a skeletal muscle subtype of ryanodine receptors that stabilizes intracellular calcium concentrations and exerts neuroprotective effects in neurons submitted to excitotoxic challenges. The mechanisms of dantrolene-induced neuroprotection are not clear. In this study, using a model of cultured rat cerebellar granule neurons, we demonstrated that dantrolene inhibits NMDA-evoked 45Ca uptake, indicating that this drug may inhibit the activity of NMDA receptor channels. Primary neuronal cultures were incubated for 10min in Mg2+-free ionic medium with NMDA and 45Ca in the presence of different concentrations of dantrolene, then radioactivity in neurons was measured by liquid scintillation spectroscopy. The results demonstrated that dantrolene, applied at micromolar concentrations, inhibits NMDA-evoked 45Ca uptake in neurons in a dose-dependent manner. DMSO, a vehicle to dantrolene, in concentrations used in this study had no effect on NMDA-evoked 45Ca uptake. 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| subjects | [formula omitted] uptake Animals Biological and medical sciences Calcium - metabolism Cells, Cultured Cerebellar granule neurons Cerebellum - metabolism Cerebellum - physiology Cytoplasmic Granules - metabolism Cytoplasmic Granules - physiology Dantrolene Dantrolene - pharmacology DMSO Fundamental and applied biological sciences. Psychology N-Methylaspartate - antagonists & inhibitors N-Methylaspartate - physiology NMDA receptors Rats |
| title | Dantrolene inhibits NMDA-induced 45Ca uptake in cultured cerebellar granule neurons |
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