Purine uptake and release in rat C6 glioma cells: nucleoside transport and purine metabolism under ATP-depleting conditions.
Identifieur interne : 003362 ( Main/Exploration ); précédent : 003361; suivant : 003363Purine uptake and release in rat C6 glioma cells: nucleoside transport and purine metabolism under ATP-depleting conditions.
Auteurs : C J Sinclair [Canada] ; C G Larivière ; J D Young ; C E Cass ; S A Baldwin ; F E ParkinsonSource :
- Journal of neurochemistry [ 0022-3042 ] ; 2000.
English descriptors
- KwdEn :
- AMP Deaminase (antagonists & inhibitors), Adenine (metabolism), Adenosine (metabolism), Adenosine (pharmacokinetics), Adenosine Triphosphate (metabolism), Animals, Carrier Proteins (genetics), Carrier Proteins (metabolism), Dose-Response Relationship, Drug, Enzyme Inhibitors (pharmacology), Equilibrative Nucleoside Transport Proteins, Equilibrative-Nucleoside Transporter 2, Formycins (metabolism), Formycins (pharmacokinetics), Glioma (metabolism), Glioma (pathology), Hypoxanthine (metabolism), Inosine (metabolism), Iodoacetates (pharmacology), Nucleosides (metabolism), Nucleosides (pharmacokinetics), Phosphodiesterase Inhibitors (pharmacology), Purines (metabolism), Purines (pharmacokinetics), Rats, Reverse Transcriptase Polymerase Chain Reaction, Sodium (metabolism), Sodium Cyanide (pharmacology), Thioinosine (analogs & derivatives), Tumor Cells, Cultured.
- MESH :
- chemical , analogs & derivatives : Thioinosine.
- chemical , antagonists & inhibitors : AMP Deaminase.
- chemical , genetics : Carrier Proteins.
- chemical , metabolism : Adenine, Adenosine, Adenosine Triphosphate, Carrier Proteins, Formycins, Hypoxanthine, Inosine, Nucleosides, Purines, Sodium.
- chemical , pharmacokinetics : Adenosine, Formycins, Nucleosides, Purines.
- chemical , pharmacology : Enzyme Inhibitors, Iodoacetates, Phosphodiesterase Inhibitors, Sodium Cyanide.
- metabolism : Glioma.
- pathology : Glioma.
- Animals, Dose-Response Relationship, Drug, Equilibrative Nucleoside Transport Proteins, Equilibrative-Nucleoside Transporter 2, Rats, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured.
Abstract
Adenosine, through activation of membrane-bound receptors, has been reported to have neuroprotective properties during strokes or seizures. The role of astrocytes in regulating brain interstitial adenosine levels has not been clearly defined. We have determined the nucleoside transporters present in rat C6 glioma cells. RT-PCR analysis, (3)H-nucleoside uptake experiments, and [(3)H]nitrobenzylthioinosine ([(3)H]NBMPR) binding assays indicated that the primary functional nucleoside transporter in C6 cells was rENT2, an equilibrative nucleoside transporter (ENT) that is relatively insensitive to inhibition by NBMPR. [(3)H]Formycin B, a poorly metabolized nucleoside analogue, was used to investigate nucleoside release processes, and rENT2 transporters mediated [(3)H]formycin B release from these cells. Adenosine release was investigated by first loading cells with [(3)H]adenine to label adenine nucleotide pools. Tritium release was initiated by inhibiting glycolytic and oxidative ATP generation and thus depleting ATP levels. Our results indicate that during ATP-depleting conditions, AMP catabolism progressed via the reactions AMP --> IMP --> inosine --> hypoxanthine, which accounted for >90% of the evoked tritium release. It was surprising that adenosine was not released during ATP-depleting conditions unless AMP deaminase and adenosine deaminase were inhibited. Inosine release was enhanced by inhibition of purine nucleoside phosphorylase; ENT2 transporters mediated the release of adenosine or inosine. However, inhibition of AMP deaminase/adenosine deaminase or purine nucleoside phosphorylase during ATP depletion produced release of adenosine or inosine, respectively, via the rENT2 transporter. This indicates that C6 glioma cells possess primarily rENT2 nucleoside transporters that function in adenosine uptake but that intracellular metabolism prevents the release of adenosine from these cells even during ATP-depleting conditions.
PubMed: 10987833
Affiliations:
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Le document en format XML
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sortKey="Young, J D" sort="Young, J D" uniqKey="Young J" first="J D" last="Young">J D Young</name></author><author><name sortKey="Cass, C E" sort="Cass, C E" uniqKey="Cass C" first="C E" last="Cass">C E Cass</name></author><author><name sortKey="Baldwin, S A" sort="Baldwin, S A" uniqKey="Baldwin S" first="S A" last="Baldwin">S A Baldwin</name></author><author><name sortKey="Parkinson, F E" sort="Parkinson, F E" uniqKey="Parkinson F" first="F E" last="Parkinson">F E Parkinson</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2000">2000</date><idno type="RBID">pubmed:10987833</idno><idno type="pmid">10987833</idno><idno type="wicri:Area/PubMed/Corpus">001615</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001615</idno><idno type="wicri:Area/PubMed/Curation">001615</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001615</idno><idno 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Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Lariviere, C G" sort="Lariviere, C G" uniqKey="Lariviere C" first="C G" last="Larivière">C G Larivière</name></author><author><name sortKey="Young, J D" sort="Young, J D" uniqKey="Young J" first="J D" last="Young">J D Young</name></author><author><name sortKey="Cass, C E" sort="Cass, C E" uniqKey="Cass C" first="C E" last="Cass">C E Cass</name></author><author><name sortKey="Baldwin, S A" sort="Baldwin, S A" uniqKey="Baldwin S" first="S A" last="Baldwin">S A Baldwin</name></author><author><name sortKey="Parkinson, F E" sort="Parkinson, F E" uniqKey="Parkinson F" first="F E" last="Parkinson">F E Parkinson</name></author></analytic><series><title level="j">Journal of neurochemistry</title><idno type="ISSN">0022-3042</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMP Deaminase (antagonists & inhibitors)</term><term>Adenine (metabolism)</term><term>Adenosine (metabolism)</term><term>Adenosine (pharmacokinetics)</term><term>Adenosine Triphosphate (metabolism)</term><term>Animals</term><term>Carrier Proteins (genetics)</term><term>Carrier Proteins (metabolism)</term><term>Dose-Response Relationship, Drug</term><term>Enzyme Inhibitors (pharmacology)</term><term>Equilibrative Nucleoside Transport Proteins</term><term>Equilibrative-Nucleoside Transporter 2</term><term>Formycins (metabolism)</term><term>Formycins (pharmacokinetics)</term><term>Glioma (metabolism)</term><term>Glioma (pathology)</term><term>Hypoxanthine (metabolism)</term><term>Inosine (metabolism)</term><term>Iodoacetates (pharmacology)</term><term>Nucleosides (metabolism)</term><term>Nucleosides (pharmacokinetics)</term><term>Phosphodiesterase Inhibitors (pharmacology)</term><term>Purines (metabolism)</term><term>Purines (pharmacokinetics)</term><term>Rats</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Sodium (metabolism)</term><term>Sodium Cyanide (pharmacology)</term><term>Thioinosine (analogs & derivatives)</term><term>Tumor Cells, Cultured</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Thioinosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>AMP Deaminase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Carrier Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenine</term><term>Adenosine</term><term>Adenosine Triphosphate</term><term>Carrier Proteins</term><term>Formycins</term><term>Hypoxanthine</term><term>Inosine</term><term>Nucleosides</term><term>Purines</term><term>Sodium</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Adenosine</term><term>Formycins</term><term>Nucleosides</term><term>Purines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Enzyme Inhibitors</term><term>Iodoacetates</term><term>Phosphodiesterase Inhibitors</term><term>Sodium Cyanide</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Glioma</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Glioma</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Dose-Response Relationship, Drug</term><term>Equilibrative Nucleoside Transport Proteins</term><term>Equilibrative-Nucleoside Transporter 2</term><term>Rats</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Tumor Cells, Cultured</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Adenosine, through activation of membrane-bound receptors, has been reported to have neuroprotective properties during strokes or seizures. The role of astrocytes in regulating brain interstitial adenosine levels has not been clearly defined. We have determined the nucleoside transporters present in rat C6 glioma cells. RT-PCR analysis, (3)H-nucleoside uptake experiments, and [(3)H]nitrobenzylthioinosine ([(3)H]NBMPR) binding assays indicated that the primary functional nucleoside transporter in C6 cells was rENT2, an equilibrative nucleoside transporter (ENT) that is relatively insensitive to inhibition by NBMPR. [(3)H]Formycin B, a poorly metabolized nucleoside analogue, was used to investigate nucleoside release processes, and rENT2 transporters mediated [(3)H]formycin B release from these cells. Adenosine release was investigated by first loading cells with [(3)H]adenine to label adenine nucleotide pools. Tritium release was initiated by inhibiting glycolytic and oxidative ATP generation and thus depleting ATP levels. Our results indicate that during ATP-depleting conditions, AMP catabolism progressed via the reactions AMP --> IMP --> inosine --> hypoxanthine, which accounted for >90% of the evoked tritium release. It was surprising that adenosine was not released during ATP-depleting conditions unless AMP deaminase and adenosine deaminase were inhibited. Inosine release was enhanced by inhibition of purine nucleoside phosphorylase; ENT2 transporters mediated the release of adenosine or inosine. However, inhibition of AMP deaminase/adenosine deaminase or purine nucleoside phosphorylase during ATP depletion produced release of adenosine or inosine, respectively, via the rENT2 transporter. This indicates that C6 glioma cells possess primarily rENT2 nucleoside transporters that function in adenosine uptake but that intracellular metabolism prevents the release of adenosine from these cells even during ATP-depleting conditions.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Manitoba</li></region><settlement><li>Winnipeg</li></settlement><orgName><li>Université du Manitoba</li></orgName></list><tree><noCountry><name sortKey="Baldwin, S A" sort="Baldwin, S A" uniqKey="Baldwin S" first="S A" last="Baldwin">S A Baldwin</name><name sortKey="Cass, C E" sort="Cass, C E" uniqKey="Cass C" first="C E" last="Cass">C E Cass</name><name sortKey="Lariviere, C G" sort="Lariviere, C G" uniqKey="Lariviere C" first="C G" last="Larivière">C G Larivière</name><name sortKey="Parkinson, F E" sort="Parkinson, F E" uniqKey="Parkinson F" first="F E" last="Parkinson">F E Parkinson</name><name sortKey="Young, J D" sort="Young, J D" uniqKey="Young J" first="J D" last="Young">J D Young</name></noCountry><country name="Canada"><region name="Manitoba"><name sortKey="Sinclair, C J" sort="Sinclair, C J" uniqKey="Sinclair C" first="C J" last="Sinclair">C J Sinclair</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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