N-methyl-D-aspartate-evoked adenosine and inosine release from neurons requires extracellular calcium.
Identifieur interne : 000E30 ( PubMed/Corpus ); précédent : 000E29; suivant : 000E31N-methyl-D-aspartate-evoked adenosine and inosine release from neurons requires extracellular calcium.
Auteurs : Christina R. Zamzow ; Ratna Bose ; Fiona E. ParkinsonSource :
- Canadian journal of physiology and pharmacology [ 1205-7541 ] ; 2009.
English descriptors
- KwdEn :
- Adenosine (metabolism), Animals, Calcium (physiology), Calcium Signaling (drug effects), Calcium-Calmodulin-Dependent Protein Kinase Type 2 (physiology), Cerebral Cortex (drug effects), Cerebral Cortex (metabolism), Chelating Agents (pharmacology), Dizocilpine Maleate (pharmacology), Egtazic Acid (analogs & derivatives), Egtazic Acid (pharmacology), Excitatory Amino Acid Antagonists (pharmacology), Inosine (metabolism), N-Methylaspartate (pharmacology), Neurons (drug effects), Neurons (metabolism), Piperidines (pharmacology), Purines (pharmacology), Quinoxalines (pharmacology), Rats, Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors), Receptors, N-Methyl-D-Aspartate (physiology).
- MESH :
- chemical , analogs & derivatives : Egtazic Acid.
- chemical , antagonists & inhibitors : Receptors, N-Methyl-D-Aspartate.
- chemical , metabolism : Adenosine, Inosine.
- chemical , pharmacology : Chelating Agents, Dizocilpine Maleate, Egtazic Acid, Excitatory Amino Acid Antagonists, N-Methylaspartate, Piperidines, Purines, Quinoxalines.
- chemical , physiology : Calcium, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Receptors, N-Methyl-D-Aspartate.
- drug effects : Calcium Signaling, Cerebral Cortex, Neurons.
- metabolism : Cerebral Cortex, Neurons.
- Animals, Rats.
Abstract
The nucleoside adenosine (ADO) is a neuromodulator in brain. ADO and its metabolite inosine (INO) have been shown to increase cell viability in stroke models. During ischemia, extracellular levels of both ADO and INO are increased. In this study, we treated rat cortical neurons with N-methyl-D-aspartate (NMDA) to initiate excitotoxicity and then investigated the mechanisms of ADO and INO release. NMDA induced a significant increase in ADO and INO production. The effect of NMDA receptor antagonists on NMDA-evoked ADO and INO release was examined. MK-801 (1 micromol/L), a potent antagonist that lacks receptor subunit selectivity, completely blocked evoked release of both ADO and INO. Memantine (10 micromol/L), a lower affinity antagonist that also lacks subunit selectivity, blocked INO, but not ADO, release. Ifenprodil (10 micromol/L), an inhibitor selective for NMDA receptors containing the NR2B subunit, completely blocked evoked ADO and INO release. NVP-AAM077 (NVP, 0.4 micromol/L), an inhibitor selective for NMDA receptors containing the NR2A subunit, did not significantly block evoked release of either ADO or INO. Removal of extracellular Ca2+ abolished NMDA-evoked release of both ADO and INO. BAPTA (25 micromol/L), which chelates intracellular Ca2+, had no significant effect on either ADO or INO release unless extracellular Ca2+ was also removed. Inhibitors of Ca2+/calmodulin-dependent protein kinase II (CaMKII) prevented NMDA-evoked ADO and INO release and decreased nucleoside transporter function. These data indicate that NMDA-evoked ADO and INO release is dependent on subunit composition of NMDA receptors. As well, NMDA-evoked ADO and INO release requires nucleoside transporters and extracellular Ca2+ and is enhanced by activation of CaMKII.
DOI: 10.1139/Y09-075
PubMed: 20052011
Links to Exploration step
pubmed:20052011Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">N-methyl-D-aspartate-evoked adenosine and inosine release from neurons requires extracellular calcium.</title><author><name sortKey="Zamzow, Christina R" sort="Zamzow, Christina R" uniqKey="Zamzow C" first="Christina R" last="Zamzow">Christina R. Zamzow</name><affiliation><nlm:affiliation>Department of Pharmacology and Therapeutics, A402-753 McDermot Avenue, University of Manitoba, Winnipeg, MB R3E 0T6, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Bose, Ratna" sort="Bose, Ratna" uniqKey="Bose R" first="Ratna" last="Bose">Ratna Bose</name></author><author><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E" last="Parkinson">Fiona E. Parkinson</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2009">2009</date><idno type="RBID">pubmed:20052011</idno><idno type="pmid">20052011</idno><idno type="doi">10.1139/Y09-075</idno><idno type="wicri:Area/PubMed/Corpus">000E30</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000E30</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">N-methyl-D-aspartate-evoked adenosine and inosine release from neurons requires extracellular calcium.</title><author><name sortKey="Zamzow, Christina R" sort="Zamzow, Christina R" uniqKey="Zamzow C" first="Christina R" last="Zamzow">Christina R. Zamzow</name><affiliation><nlm:affiliation>Department of Pharmacology and Therapeutics, A402-753 McDermot Avenue, University of Manitoba, Winnipeg, MB R3E 0T6, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Bose, Ratna" sort="Bose, Ratna" uniqKey="Bose R" first="Ratna" last="Bose">Ratna Bose</name></author><author><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E" last="Parkinson">Fiona E. Parkinson</name></author></analytic><series><title level="j">Canadian journal of physiology and pharmacology</title><idno type="eISSN">1205-7541</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine (metabolism)</term><term>Animals</term><term>Calcium (physiology)</term><term>Calcium Signaling (drug effects)</term><term>Calcium-Calmodulin-Dependent Protein Kinase Type 2 (physiology)</term><term>Cerebral Cortex (drug effects)</term><term>Cerebral Cortex (metabolism)</term><term>Chelating Agents (pharmacology)</term><term>Dizocilpine Maleate (pharmacology)</term><term>Egtazic Acid (analogs & derivatives)</term><term>Egtazic Acid (pharmacology)</term><term>Excitatory Amino Acid Antagonists (pharmacology)</term><term>Inosine (metabolism)</term><term>N-Methylaspartate (pharmacology)</term><term>Neurons (drug effects)</term><term>Neurons (metabolism)</term><term>Piperidines (pharmacology)</term><term>Purines (pharmacology)</term><term>Quinoxalines (pharmacology)</term><term>Rats</term><term>Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)</term><term>Receptors, N-Methyl-D-Aspartate (physiology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Egtazic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Receptors, N-Methyl-D-Aspartate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine</term><term>Inosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Chelating Agents</term><term>Dizocilpine Maleate</term><term>Egtazic Acid</term><term>Excitatory Amino Acid Antagonists</term><term>N-Methylaspartate</term><term>Piperidines</term><term>Purines</term><term>Quinoxalines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Calcium</term><term>Calcium-Calmodulin-Dependent Protein Kinase Type 2</term><term>Receptors, N-Methyl-D-Aspartate</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Calcium Signaling</term><term>Cerebral Cortex</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cerebral Cortex</term><term>Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Rats</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The nucleoside adenosine (ADO) is a neuromodulator in brain. ADO and its metabolite inosine (INO) have been shown to increase cell viability in stroke models. During ischemia, extracellular levels of both ADO and INO are increased. In this study, we treated rat cortical neurons with N-methyl-D-aspartate (NMDA) to initiate excitotoxicity and then investigated the mechanisms of ADO and INO release. NMDA induced a significant increase in ADO and INO production. The effect of NMDA receptor antagonists on NMDA-evoked ADO and INO release was examined. MK-801 (1 micromol/L), a potent antagonist that lacks receptor subunit selectivity, completely blocked evoked release of both ADO and INO. Memantine (10 micromol/L), a lower affinity antagonist that also lacks subunit selectivity, blocked INO, but not ADO, release. Ifenprodil (10 micromol/L), an inhibitor selective for NMDA receptors containing the NR2B subunit, completely blocked evoked ADO and INO release. NVP-AAM077 (NVP, 0.4 micromol/L), an inhibitor selective for NMDA receptors containing the NR2A subunit, did not significantly block evoked release of either ADO or INO. Removal of extracellular Ca2+ abolished NMDA-evoked release of both ADO and INO. BAPTA (25 micromol/L), which chelates intracellular Ca2+, had no significant effect on either ADO or INO release unless extracellular Ca2+ was also removed. Inhibitors of Ca2+/calmodulin-dependent protein kinase II (CaMKII) prevented NMDA-evoked ADO and INO release and decreased nucleoside transporter function. These data indicate that NMDA-evoked ADO and INO release is dependent on subunit composition of NMDA receptors. As well, NMDA-evoked ADO and INO release requires nucleoside transporters and extracellular Ca2+ and is enhanced by activation of CaMKII.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20052011</PMID><DateCreated><Year>2010</Year><Month>01</Month><Day>06</Day></DateCreated><DateCompleted><Year>2010</Year><Month>03</Month><Day>01</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1205-7541</ISSN><JournalIssue CitedMedium="Internet"><Volume>87</Volume><Issue>10</Issue><PubDate><Year>2009</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Canadian journal of physiology and pharmacology</Title><ISOAbbreviation>Can. J. Physiol. Pharmacol.</ISOAbbreviation></Journal><ArticleTitle>N-methyl-D-aspartate-evoked adenosine and inosine release from neurons requires extracellular calcium.</ArticleTitle><Pagination><MedlinePgn>850-8</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1139/Y09-075</ELocationID><Abstract><AbstractText>The nucleoside adenosine (ADO) is a neuromodulator in brain. ADO and its metabolite inosine (INO) have been shown to increase cell viability in stroke models. During ischemia, extracellular levels of both ADO and INO are increased. In this study, we treated rat cortical neurons with N-methyl-D-aspartate (NMDA) to initiate excitotoxicity and then investigated the mechanisms of ADO and INO release. NMDA induced a significant increase in ADO and INO production. The effect of NMDA receptor antagonists on NMDA-evoked ADO and INO release was examined. MK-801 (1 micromol/L), a potent antagonist that lacks receptor subunit selectivity, completely blocked evoked release of both ADO and INO. Memantine (10 micromol/L), a lower affinity antagonist that also lacks subunit selectivity, blocked INO, but not ADO, release. Ifenprodil (10 micromol/L), an inhibitor selective for NMDA receptors containing the NR2B subunit, completely blocked evoked ADO and INO release. NVP-AAM077 (NVP, 0.4 micromol/L), an inhibitor selective for NMDA receptors containing the NR2A subunit, did not significantly block evoked release of either ADO or INO. Removal of extracellular Ca2+ abolished NMDA-evoked release of both ADO and INO. BAPTA (25 micromol/L), which chelates intracellular Ca2+, had no significant effect on either ADO or INO release unless extracellular Ca2+ was also removed. Inhibitors of Ca2+/calmodulin-dependent protein kinase II (CaMKII) prevented NMDA-evoked ADO and INO release and decreased nucleoside transporter function. These data indicate that NMDA-evoked ADO and INO release is dependent on subunit composition of NMDA receptors. 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Maleate</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.17</RegistryNumber><NameOfSubstance UI="D054732">Calcium-Calmodulin-Dependent Protein Kinase Type 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>K22DDW77C0</RegistryNumber><NameOfSubstance UI="C025603">1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>K72T3FS567</RegistryNumber><NameOfSubstance UI="D000241">Adenosine</NameOfSubstance></Chemical><Chemical><RegistryNumber>R8OE3P6O5S</RegistryNumber><NameOfSubstance UI="C010739">ifenprodil</NameOfSubstance></Chemical><Chemical><RegistryNumber>SY7Q814VUP</RegistryNumber><NameOfSubstance UI="D002118">Calcium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000241" MajorTopicYN="N">Adenosine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName 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MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016291" MajorTopicYN="N">Dizocilpine Maleate</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004533" MajorTopicYN="N">Egtazic Acid</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018691" MajorTopicYN="N">Excitatory Amino Acid Antagonists</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007288" MajorTopicYN="N">Inosine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016202" MajorTopicYN="N">N-Methylaspartate</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009474" MajorTopicYN="N">Neurons</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010880" MajorTopicYN="N">Piperidines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011687" MajorTopicYN="N">Purines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011810" MajorTopicYN="N">Quinoxalines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016194" MajorTopicYN="N">Receptors, N-Methyl-D-Aspartate</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>1</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>1</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>3</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20052011</ArticleId><ArticleId IdType="pii">y09-075</ArticleId><ArticleId IdType="doi">10.1139/Y09-075</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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