Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippocampal slices exposed to hypoxia/reoxygenation
Major interest is currently focused on the development and evaluation of effective strategies for the pharmacological therapy of human stroke and cerebral ischemia, as well as some neurodegenerative disorders in which increased production of free oxygen radicals and the neurotoxic effect of excitato...
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| Veröffentlicht in: | Methods and Findings in Experimental and Clinical Pharmacology 2003, Vol.25 (1), p.17-25 |
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| creator | GASPAROVA-KVALTINOVA, Z STOLE, S |
| description | Major interest is currently focused on the development and evaluation of effective strategies for the pharmacological therapy of human stroke and cerebral ischemia, as well as some neurodegenerative disorders in which increased production of free oxygen radicals and the neurotoxic effect of excitatory amino acids may take place. Selected N-methyl-D-aspartate (NMDA) antagonists and antioxidants in the model of experimental oxidative stress induced by hypoxia and reoxygenation in rat hippocampal slices were tested. The putative antiglutamatergic effect of the antioxidant stobadine and its neuroprotective effect during oxidative stress was studied. NMDA antaonists 2-amino-5-phosphonovaleric acid (APV) and Mg2+, as well as the antioxidants stobadine and trolox, prevented the decrease of NMDA binding site number induced by hypoxia/reoxygenation in rat hippocampal slices. Moreover, stobadine, APV and Mg2+ prevented the decrease of NMDA binding site number due to glutamic acid incubation. Stobadine does not inhibit [3H]-glutamate binding and therefore does not seem to interact directly with glutamate binding sites. Thus, its neuroprotective effect in rat hippocampus exposed to hypoxia/reoxygenation does not seem to be based on a direct antiglutamatergic effect. The protective action of stobadine against the decrease of NMDA binding site number elicited by hypoxia/reoxygenation in rat hippocampus could rather be due to its antioxidant and antiradical effect. |
| doi_str_mv | 10.1358/mf.2003.25.1.772543 |
| format | Article |
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Selected N-methyl-D-aspartate (NMDA) antagonists and antioxidants in the model of experimental oxidative stress induced by hypoxia and reoxygenation in rat hippocampal slices were tested. The putative antiglutamatergic effect of the antioxidant stobadine and its neuroprotective effect during oxidative stress was studied. NMDA antaonists 2-amino-5-phosphonovaleric acid (APV) and Mg2+, as well as the antioxidants stobadine and trolox, prevented the decrease of NMDA binding site number induced by hypoxia/reoxygenation in rat hippocampal slices. Moreover, stobadine, APV and Mg2+ prevented the decrease of NMDA binding site number due to glutamic acid incubation. Stobadine does not inhibit [3H]-glutamate binding and therefore does not seem to interact directly with glutamate binding sites. Thus, its neuroprotective effect in rat hippocampus exposed to hypoxia/reoxygenation does not seem to be based on a direct antiglutamatergic effect. The protective action of stobadine against the decrease of NMDA binding site number elicited by hypoxia/reoxygenation in rat hippocampus could rather be due to its antioxidant and antiradical effect.</description><identifier>ISSN: 0379-0355</identifier><identifier>ISSN: 2013-0155</identifier><identifier>DOI: 10.1358/mf.2003.25.1.772543</identifier><identifier>PMID: 12690702</identifier><language>eng</language><publisher>Barcelona: Prous</publisher><subject>Animals ; Antioxidants - metabolism ; Antioxidants - pharmacology ; Binding Sites - drug effects ; Binding Sites - physiology ; Biological and medical sciences ; Cell Hypoxia - drug effects ; Cell Hypoxia - physiology ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists - metabolism ; Excitatory Amino Acid Antagonists - pharmacology ; Glutamatergic system (aspartate and other excitatory aminoacids) ; Hippocampus - drug effects ; Hippocampus - metabolism ; In Vitro Techniques ; Male ; Medical sciences ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate - metabolism</subject><ispartof>Methods and Findings in Experimental and Clinical Pharmacology, 2003, Vol.25 (1), p.17-25</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c331t-2684499b52d3c8984406e448b504215c83f20eca7fbe3de53357d69e20c705953</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14695223$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12690702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GASPAROVA-KVALTINOVA, Z</creatorcontrib><creatorcontrib>STOLE, S</creatorcontrib><title>Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippocampal slices exposed to hypoxia/reoxygenation</title><title>Methods and Findings in Experimental and Clinical Pharmacology</title><addtitle>Methods Find Exp Clin Pharmacol</addtitle><description>Major interest is currently focused on the development and evaluation of effective strategies for the pharmacological therapy of human stroke and cerebral ischemia, as well as some neurodegenerative disorders in which increased production of free oxygen radicals and the neurotoxic effect of excitatory amino acids may take place. Selected N-methyl-D-aspartate (NMDA) antagonists and antioxidants in the model of experimental oxidative stress induced by hypoxia and reoxygenation in rat hippocampal slices were tested. The putative antiglutamatergic effect of the antioxidant stobadine and its neuroprotective effect during oxidative stress was studied. NMDA antaonists 2-amino-5-phosphonovaleric acid (APV) and Mg2+, as well as the antioxidants stobadine and trolox, prevented the decrease of NMDA binding site number induced by hypoxia/reoxygenation in rat hippocampal slices. Moreover, stobadine, APV and Mg2+ prevented the decrease of NMDA binding site number due to glutamic acid incubation. Stobadine does not inhibit [3H]-glutamate binding and therefore does not seem to interact directly with glutamate binding sites. Thus, its neuroprotective effect in rat hippocampus exposed to hypoxia/reoxygenation does not seem to be based on a direct antiglutamatergic effect. The protective action of stobadine against the decrease of NMDA binding site number elicited by hypoxia/reoxygenation in rat hippocampus could rather be due to its antioxidant and antiradical effect.</description><subject>Animals</subject><subject>Antioxidants - metabolism</subject><subject>Antioxidants - pharmacology</subject><subject>Binding Sites - drug effects</subject><subject>Binding Sites - physiology</subject><subject>Biological and medical sciences</subject><subject>Cell Hypoxia - drug effects</subject><subject>Cell Hypoxia - physiology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Excitatory Amino Acid Antagonists - metabolism</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Glutamatergic system (aspartate and other excitatory aminoacids)</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><issn>0379-0355</issn><issn>2013-0155</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUMtOwzAQ9AFES-ELkJAvHJM63jiPY1XKQypwgXPk-NEaJXYUB6n5Bn4ah1bqaTWzMzvaQeguIXECrFi2OqaEQExZnMR5TlkKF2hOIC8jAozN0LX334TQhAG7QrOEZiXJCZ2j343WSgzYacztYNzByDB9ABK_vz2uJpbvnDU-kM7iYa-wVNabYZw8_5LaWGnsDgdSeWws7vmA96brnOBtxxvsGyPCRh0655XEg8P7sQtRfNkrdxh3yvIQbW_QpeaNV7enuUBfT5vP9Uu0_Xh-Xa-2kQBIhohmRZqWZc2oBFGUAZBMpWlRM5KGB0UBmhIleK5rBVIxAJbLrFSUiJywksECwfGu6J33vdJV15uW92OVkGqqs2p1NdVZUVYl1bHO4Lo_urqfulXy7Dl1GQQPJwH3gje651YYf9alWckoBfgDYpKBRw</recordid><startdate>2003</startdate><enddate>2003</enddate><creator>GASPAROVA-KVALTINOVA, Z</creator><creator>STOLE, S</creator><general>Prous</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></search><sort><creationdate>2003</creationdate><title>Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippocampal slices exposed to hypoxia/reoxygenation</title><author>GASPAROVA-KVALTINOVA, Z ; STOLE, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c331t-2684499b52d3c8984406e448b504215c83f20eca7fbe3de53357d69e20c705953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Antioxidants - metabolism</topic><topic>Antioxidants - pharmacology</topic><topic>Binding Sites - drug effects</topic><topic>Binding Sites - physiology</topic><topic>Biological and medical sciences</topic><topic>Cell Hypoxia - drug effects</topic><topic>Cell Hypoxia - physiology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Excitatory Amino Acid Antagonists - metabolism</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Glutamatergic system (aspartate and other excitatory aminoacids)</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GASPAROVA-KVALTINOVA, Z</creatorcontrib><creatorcontrib>STOLE, S</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><jtitle>Methods and Findings in Experimental and Clinical Pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GASPAROVA-KVALTINOVA, Z</au><au>STOLE, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippocampal slices exposed to hypoxia/reoxygenation</atitle><jtitle>Methods and Findings in Experimental and Clinical Pharmacology</jtitle><addtitle>Methods Find Exp Clin Pharmacol</addtitle><date>2003</date><risdate>2003</risdate><volume>25</volume><issue>1</issue><spage>17</spage><epage>25</epage><pages>17-25</pages><issn>0379-0355</issn><issn>2013-0155</issn><abstract>Major interest is currently focused on the development and evaluation of effective strategies for the pharmacological therapy of human stroke and cerebral ischemia, as well as some neurodegenerative disorders in which increased production of free oxygen radicals and the neurotoxic effect of excitatory amino acids may take place. Selected N-methyl-D-aspartate (NMDA) antagonists and antioxidants in the model of experimental oxidative stress induced by hypoxia and reoxygenation in rat hippocampal slices were tested. The putative antiglutamatergic effect of the antioxidant stobadine and its neuroprotective effect during oxidative stress was studied. NMDA antaonists 2-amino-5-phosphonovaleric acid (APV) and Mg2+, as well as the antioxidants stobadine and trolox, prevented the decrease of NMDA binding site number induced by hypoxia/reoxygenation in rat hippocampal slices. Moreover, stobadine, APV and Mg2+ prevented the decrease of NMDA binding site number due to glutamic acid incubation. Stobadine does not inhibit [3H]-glutamate binding and therefore does not seem to interact directly with glutamate binding sites. Thus, its neuroprotective effect in rat hippocampus exposed to hypoxia/reoxygenation does not seem to be based on a direct antiglutamatergic effect. The protective action of stobadine against the decrease of NMDA binding site number elicited by hypoxia/reoxygenation in rat hippocampus could rather be due to its antioxidant and antiradical effect.</abstract><cop>Barcelona</cop><pub>Prous</pub><pmid>12690702</pmid><doi>10.1358/mf.2003.25.1.772543</doi><tpages>9</tpages></addata></record> |
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| source | MEDLINE; Portico (Triggered Content) Journals |
| subjects | Animals Antioxidants - metabolism Antioxidants - pharmacology Binding Sites - drug effects Binding Sites - physiology Biological and medical sciences Cell Hypoxia - drug effects Cell Hypoxia - physiology Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists - metabolism Excitatory Amino Acid Antagonists - pharmacology Glutamatergic system (aspartate and other excitatory aminoacids) Hippocampus - drug effects Hippocampus - metabolism In Vitro Techniques Male Medical sciences Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Rats Rats, Wistar Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - metabolism |
| title | Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippocampal slices exposed to hypoxia/reoxygenation |
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