Transgenic expression of human equilibrative nucleoside transporter 1 in mouse neurons.
Identifieur interne : 001D56 ( Main/Exploration ); précédent : 001D55; suivant : 001D57Transgenic expression of human equilibrative nucleoside transporter 1 in mouse neurons.
Auteurs : Fiona E. Parkinson [Canada] ; Wei Xiong ; Christina R. Zamzow ; Taeyo Chestley ; Tooru Mizuno ; Mary Lynn DuckworthSource :
- Journal of neurochemistry [ 1471-4159 ] ; 2009.
English descriptors
- KwdEn :
- Adenosine (metabolism), Animals, Behavior, Animal (drug effects), Behavior, Animal (physiology), Caffeine (administration & dosage), Caffeine (antagonists & inhibitors), Equilibrative Nucleoside Transporter 1 (biosynthesis), Equilibrative Nucleoside Transporter 1 (genetics), Equilibrative Nucleoside Transporter 1 (physiology), Ethanol (administration & dosage), Gene Expression Regulation (drug effects), Gene Expression Regulation (physiology), Humans, Mice, Mice, Transgenic, Neurons (drug effects), Neurons (metabolism), Neurons (physiology), PC12 Cells, Rats, Receptors, Purinergic P1 (biosynthesis), Receptors, Purinergic P1 (genetics), Up-Regulation (genetics).
- MESH :
- chemical , administration & dosage : Caffeine, Ethanol.
- chemical , antagonists & inhibitors : Caffeine.
- chemical , biosynthesis : Equilibrative Nucleoside Transporter 1, Receptors, Purinergic P1.
- chemical , genetics : Equilibrative Nucleoside Transporter 1, Receptors, Purinergic P1.
- chemical , metabolism : Adenosine.
- drug effects : Behavior, Animal, Gene Expression Regulation, Neurons.
- genetics : Up-Regulation.
- metabolism : Neurons.
- physiology : Behavior, Animal, Equilibrative Nucleoside Transporter 1, Gene Expression Regulation, Neurons.
- Animals, Humans, Mice, Mice, Transgenic, PC12 Cells, Rats.
Abstract
Transgenic mice that express human equilibrative nucleoside transporter subtype 1 (hENT1) under the control of a neuron-specific enolase promoter have been generated. Southern blot and PCR revealed the presence of the transgene in five founder mice. Mice from each founder line were examined by reverse transcriptase (RT)-PCR and found to express hENT1 in RNA isolated from whole brain, cerebral cortex, striatum, hippocampus, and cerebellum but not liver, kidney, heart, lung or skeletal muscle. Cortical synaptosomes prepared from transgenic mice had significantly increased [(3)H]adenosine uptake and [(3)H]nitrobenzylthioinosine binding, relative to samples from wild-type mice. In behavioral tests, transgenic mice had altered responses to caffeine and ethanol, two drugs that inhibit and enhance, respectively, adenosine receptor activity. Caffeine-induced locomotor stimulation was attenuated whereas the hypnotic effect of ethanol was enhanced in transgenic mice. Caffeine was more potent in inhibiting ethanol-induced motor incoordination in wild-type than in transgenic mice. No differences in expression of mouse genes for adenosine receptors, nucleoside transporters, or purine metabolizing enzymes were detected by RT-PCR analyses. These data indicate that expression of hENT1 in neurons does not trigger adaptive changes in expression of adenosine-related genes. Instead, hENT1 expression affects dynamic changes in endogenous adenosine levels, as revealed by altered behavioral responses to drugs that affect adenosine receptor signalling.
DOI: 10.1111/j.1471-4159.2009.05991.x
PubMed: 19222701
Affiliations:
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Parkinson</name><affiliation wicri:level="4"><nlm:affiliation>Departments of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada. parkins@cc.umanitoba.ca</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Departments 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="Xiong, Wei" sort="Xiong, Wei" uniqKey="Xiong W" first="Wei" last="Xiong">Wei Xiong</name></author><author><name sortKey="Zamzow, Christina R" sort="Zamzow, Christina R" uniqKey="Zamzow C" first="Christina R" last="Zamzow">Christina R. Zamzow</name></author><author><name sortKey="Chestley, Taeyo" sort="Chestley, Taeyo" uniqKey="Chestley T" first="Taeyo" last="Chestley">Taeyo Chestley</name></author><author><name sortKey="Mizuno, Tooru" sort="Mizuno, Tooru" uniqKey="Mizuno T" first="Tooru" last="Mizuno">Tooru Mizuno</name></author><author><name sortKey="Duckworth, Mary Lynn" sort="Duckworth, Mary Lynn" uniqKey="Duckworth M" first="Mary Lynn" last="Duckworth">Mary Lynn Duckworth</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2009">2009</date><idno type="RBID">pubmed:19222701</idno><idno type="pmid">19222701</idno><idno type="doi">10.1111/j.1471-4159.2009.05991.x</idno><idno type="wicri:Area/PubMed/Corpus">000E85</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000E85</idno><idno type="wicri:Area/PubMed/Curation">000E85</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000E85</idno><idno type="wicri:Area/PubMed/Checkpoint">000E85</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000E85</idno><idno type="wicri:Area/Ncbi/Merge">000A34</idno><idno type="wicri:Area/Ncbi/Curation">000A34</idno><idno type="wicri:Area/Ncbi/Checkpoint">000A34</idno><idno type="wicri:Area/Main/Merge">001F02</idno><idno type="wicri:Area/Main/Curation">001D56</idno><idno type="wicri:Area/Main/Exploration">001D56</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Transgenic expression of human equilibrative nucleoside transporter 1 in mouse neurons.</title><author><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E" last="Parkinson">Fiona E. Parkinson</name><affiliation wicri:level="4"><nlm:affiliation>Departments of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada. parkins@cc.umanitoba.ca</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Departments 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="Xiong, Wei" sort="Xiong, Wei" uniqKey="Xiong W" first="Wei" last="Xiong">Wei Xiong</name></author><author><name sortKey="Zamzow, Christina R" sort="Zamzow, Christina R" uniqKey="Zamzow C" first="Christina R" last="Zamzow">Christina R. Zamzow</name></author><author><name sortKey="Chestley, Taeyo" sort="Chestley, Taeyo" uniqKey="Chestley T" first="Taeyo" last="Chestley">Taeyo Chestley</name></author><author><name sortKey="Mizuno, Tooru" sort="Mizuno, Tooru" uniqKey="Mizuno T" first="Tooru" last="Mizuno">Tooru Mizuno</name></author><author><name sortKey="Duckworth, Mary Lynn" sort="Duckworth, Mary Lynn" uniqKey="Duckworth M" first="Mary Lynn" last="Duckworth">Mary Lynn Duckworth</name></author></analytic><series><title level="j">Journal of neurochemistry</title><idno type="eISSN">1471-4159</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>Behavior, Animal (drug effects)</term><term>Behavior, Animal (physiology)</term><term>Caffeine (administration & dosage)</term><term>Caffeine (antagonists & inhibitors)</term><term>Equilibrative Nucleoside Transporter 1 (biosynthesis)</term><term>Equilibrative Nucleoside Transporter 1 (genetics)</term><term>Equilibrative Nucleoside Transporter 1 (physiology)</term><term>Ethanol (administration & dosage)</term><term>Gene Expression Regulation (drug effects)</term><term>Gene Expression Regulation (physiology)</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Neurons (drug effects)</term><term>Neurons (metabolism)</term><term>Neurons (physiology)</term><term>PC12 Cells</term><term>Rats</term><term>Receptors, Purinergic P1 (biosynthesis)</term><term>Receptors, Purinergic P1 (genetics)</term><term>Up-Regulation (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Caffeine</term><term>Ethanol</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Caffeine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Equilibrative Nucleoside Transporter 1</term><term>Receptors, Purinergic P1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Equilibrative Nucleoside Transporter 1</term><term>Receptors, Purinergic P1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Behavior, Animal</term><term>Gene Expression Regulation</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Up-Regulation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Behavior, Animal</term><term>Equilibrative Nucleoside Transporter 1</term><term>Gene Expression Regulation</term><term>Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>PC12 Cells</term><term>Rats</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Transgenic mice that express human equilibrative nucleoside transporter subtype 1 (hENT1) under the control of a neuron-specific enolase promoter have been generated. Southern blot and PCR revealed the presence of the transgene in five founder mice. Mice from each founder line were examined by reverse transcriptase (RT)-PCR and found to express hENT1 in RNA isolated from whole brain, cerebral cortex, striatum, hippocampus, and cerebellum but not liver, kidney, heart, lung or skeletal muscle. Cortical synaptosomes prepared from transgenic mice had significantly increased [(3)H]adenosine uptake and [(3)H]nitrobenzylthioinosine binding, relative to samples from wild-type mice. In behavioral tests, transgenic mice had altered responses to caffeine and ethanol, two drugs that inhibit and enhance, respectively, adenosine receptor activity. Caffeine-induced locomotor stimulation was attenuated whereas the hypnotic effect of ethanol was enhanced in transgenic mice. Caffeine was more potent in inhibiting ethanol-induced motor incoordination in wild-type than in transgenic mice. No differences in expression of mouse genes for adenosine receptors, nucleoside transporters, or purine metabolizing enzymes were detected by RT-PCR analyses. These data indicate that expression of hENT1 in neurons does not trigger adaptive changes in expression of adenosine-related genes. Instead, hENT1 expression affects dynamic changes in endogenous adenosine levels, as revealed by altered behavioral responses to drugs that affect adenosine receptor signalling.</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="Chestley, Taeyo" sort="Chestley, Taeyo" uniqKey="Chestley T" first="Taeyo" last="Chestley">Taeyo Chestley</name><name sortKey="Duckworth, Mary Lynn" sort="Duckworth, Mary Lynn" uniqKey="Duckworth M" first="Mary Lynn" last="Duckworth">Mary Lynn Duckworth</name><name sortKey="Mizuno, Tooru" sort="Mizuno, Tooru" uniqKey="Mizuno T" first="Tooru" last="Mizuno">Tooru Mizuno</name><name sortKey="Xiong, Wei" sort="Xiong, Wei" uniqKey="Xiong W" first="Wei" last="Xiong">Wei Xiong</name><name sortKey="Zamzow, Christina R" sort="Zamzow, Christina R" uniqKey="Zamzow C" first="Christina R" last="Zamzow">Christina R. Zamzow</name></noCountry><country name="Canada"><region name="Manitoba"><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E" last="Parkinson">Fiona E. Parkinson</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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