Effects of nitrobenzylthioinosine on neuronal injury, adenosine levels, and adenosine receptor activity in rat forebrain ischemia.
Identifieur interne : 003373 ( Main/Exploration ); précédent : 003372; suivant : 003374Effects of nitrobenzylthioinosine on neuronal injury, adenosine levels, and adenosine receptor activity in rat forebrain ischemia.
Auteurs : F E Parkinson [Canada] ; Y W Zhang ; P N Shepel ; S C Greenway ; J. Peeling ; J D GeigerSource :
- Journal of neurochemistry [ 0022-3042 ] ; 2000.
English descriptors
- KwdEn :
- Adenosine (metabolism), Affinity Labels, Animals, Cerebral Ventricles (drug effects), Cerebral Ventricles (physiology), Gene Expression Regulation (drug effects), Injections, Intraventricular, Ischemic Attack, Transient (pathology), Ischemic Attack, Transient (physiopathology), Male, Neurons (drug effects), Neurons (pathology), Neurons (physiology), Prodrugs (administration & dosage), Prodrugs (pharmacology), Prosencephalon (metabolism), Prosencephalon (pathology), Prosencephalon (physiopathology), Pyramidal Cells (drug effects), Pyramidal Cells (pathology), Rats, Rats, Sprague-Dawley, Receptors, Purinergic P1 (drug effects), Receptors, Purinergic P1 (physiology), Reperfusion, Thioinosine (administration & dosage), Thioinosine (analogs & derivatives), Thioinosine (pharmacology), Thionucleotides (pharmacology), Transcription, Genetic (drug effects), Tumor Necrosis Factor-alpha (genetics).
- MESH :
- chemical , administration & dosage : Prodrugs, Thioinosine.
- chemical , analogs & derivatives : Thioinosine.
- chemical , drug effects : Receptors, Purinergic P1.
- chemical , genetics : Tumor Necrosis Factor-alpha.
- chemical , metabolism : Adenosine.
- chemical , pharmacology : Prodrugs, Thioinosine, Thionucleotides.
- chemical , physiology : Receptors, Purinergic P1.
- chemical : Affinity Labels.
- drug effects : Cerebral Ventricles, Gene Expression Regulation, Neurons, Pyramidal Cells, Transcription, Genetic.
- metabolism : Prosencephalon.
- pathology : Ischemic Attack, Transient, Neurons, Prosencephalon, Pyramidal Cells.
- physiology : Cerebral Ventricles, Neurons.
- physiopathology : Ischemic Attack, Transient, Prosencephalon.
- Animals, Injections, Intraventricular, Male, Rats, Rats, Sprague-Dawley, Reperfusion.
Abstract
Adenosine levels increase in brain during cerebral ischemia, and adenosine has receptor-mediated neuroprotective effects. This study was performed to test the hypothesis that nitrobenzylthioinosine (NBMPR), a selective and potent inhibitor of one adenosine transporter subtype termed ENT1, or es, can protect against ischemic neuronal injury by enhancing adenosine levels and potentiating adenosine receptor-mediated effects, including attenuation of the cellular production and release of tumor necrosis factor-alpha (TNF-alpha). In rats, the phosphorylated prodrug form of NBMPR, NBMPR-phosphate, or saline was administered by intracerebroventricular injection 30 min before forebrain ischemia. Seven days following the ischemic episode, rats were killed, and neuronal damage in the CA1 region of the hippocampus was assessed. The number of pyramidal neurons was significantly (p < 0.001) greater in the NBMPR-P treatment group. A trend toward protection was still evident at 28 days postreperfusion. Adenosine increased significantly during ischemia to levels eight- to 85-fold above basal. NBMPR-P treatment did not cause statistically significant increases in ischemic adenosine levels; however, this treatment tended to increase adenosine levels in all brain regions at 7 min postreperfusion. Ischemia-induced expression of TNF-alpha was not altered by NBMPR-P treatment, and the nonselective adenosine receptor antagonist 8-(p-sulfophenyl) theophylline did not abolish the neuroprotective effects of NBMPR-P treatment. These data indicate that NBMPR can protect CA1 pyramidal neurons from ischemic death without statistically significant effects on adenosine levels or adenosine receptor-mediated inhibition of the proinflammatory cytokine TNF-alpha.
PubMed: 10899957
Affiliations:
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Le document en format XML
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Peeling</name></author><author><name sortKey="Geiger, J D" sort="Geiger, J D" uniqKey="Geiger J" first="J D" last="Geiger">J D Geiger</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>Adenosine (metabolism)</term><term>Affinity Labels</term><term>Animals</term><term>Cerebral Ventricles (drug effects)</term><term>Cerebral Ventricles (physiology)</term><term>Gene Expression Regulation (drug effects)</term><term>Injections, Intraventricular</term><term>Ischemic Attack, Transient (pathology)</term><term>Ischemic Attack, Transient (physiopathology)</term><term>Male</term><term>Neurons (drug effects)</term><term>Neurons (pathology)</term><term>Neurons (physiology)</term><term>Prodrugs (administration & dosage)</term><term>Prodrugs (pharmacology)</term><term>Prosencephalon (metabolism)</term><term>Prosencephalon (pathology)</term><term>Prosencephalon (physiopathology)</term><term>Pyramidal Cells (drug effects)</term><term>Pyramidal Cells (pathology)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Receptors, Purinergic P1 (drug effects)</term><term>Receptors, Purinergic P1 (physiology)</term><term>Reperfusion</term><term>Thioinosine (administration & dosage)</term><term>Thioinosine (analogs & derivatives)</term><term>Thioinosine (pharmacology)</term><term>Thionucleotides (pharmacology)</term><term>Transcription, Genetic (drug effects)</term><term>Tumor Necrosis Factor-alpha (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Prodrugs</term><term>Thioinosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Thioinosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Purinergic P1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Tumor Necrosis Factor-alpha</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Prodrugs</term><term>Thioinosine</term><term>Thionucleotides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Receptors, Purinergic P1</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Affinity Labels</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cerebral Ventricles</term><term>Gene Expression Regulation</term><term>Neurons</term><term>Pyramidal Cells</term><term>Transcription, Genetic</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Prosencephalon</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Ischemic Attack, Transient</term><term>Neurons</term><term>Prosencephalon</term><term>Pyramidal Cells</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cerebral Ventricles</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Ischemic Attack, Transient</term><term>Prosencephalon</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Injections, Intraventricular</term><term>Male</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Reperfusion</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Adenosine levels increase in brain during cerebral ischemia, and adenosine has receptor-mediated neuroprotective effects. This study was performed to test the hypothesis that nitrobenzylthioinosine (NBMPR), a selective and potent inhibitor of one adenosine transporter subtype termed ENT1, or es, can protect against ischemic neuronal injury by enhancing adenosine levels and potentiating adenosine receptor-mediated effects, including attenuation of the cellular production and release of tumor necrosis factor-alpha (TNF-alpha). In rats, the phosphorylated prodrug form of NBMPR, NBMPR-phosphate, or saline was administered by intracerebroventricular injection 30 min before forebrain ischemia. Seven days following the ischemic episode, rats were killed, and neuronal damage in the CA1 region of the hippocampus was assessed. The number of pyramidal neurons was significantly (p < 0.001) greater in the NBMPR-P treatment group. A trend toward protection was still evident at 28 days postreperfusion. Adenosine increased significantly during ischemia to levels eight- to 85-fold above basal. NBMPR-P treatment did not cause statistically significant increases in ischemic adenosine levels; however, this treatment tended to increase adenosine levels in all brain regions at 7 min postreperfusion. Ischemia-induced expression of TNF-alpha was not altered by NBMPR-P treatment, and the nonselective adenosine receptor antagonist 8-(p-sulfophenyl) theophylline did not abolish the neuroprotective effects of NBMPR-P treatment. These data indicate that NBMPR can protect CA1 pyramidal neurons from ischemic death without statistically significant effects on adenosine levels or adenosine receptor-mediated inhibition of the proinflammatory cytokine TNF-alpha.</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="Geiger, J D" sort="Geiger, J D" uniqKey="Geiger J" first="J D" last="Geiger">J D Geiger</name><name sortKey="Greenway, S C" sort="Greenway, S C" uniqKey="Greenway S" first="S C" last="Greenway">S C Greenway</name><name sortKey="Peeling, J" sort="Peeling, J" uniqKey="Peeling J" first="J" last="Peeling">J. Peeling</name><name sortKey="Shepel, P N" sort="Shepel, P N" uniqKey="Shepel P" first="P N" last="Shepel">P N Shepel</name><name sortKey="Zhang, Y W" sort="Zhang, Y W" uniqKey="Zhang Y" first="Y W" last="Zhang">Y W Zhang</name></noCountry><country name="Canada"><region name="Manitoba"><name sortKey="Parkinson, F E" sort="Parkinson, F E" uniqKey="Parkinson F" first="F E" last="Parkinson">F E Parkinson</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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