Distinct regional distribution of human equilibrative nucleoside transporter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system
Identifieur interne : 003144 ( Main/Exploration ); précédent : 003143; suivant : 003145Distinct regional distribution of human equilibrative nucleoside transporter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system
Auteurs : Lori L. Jennings [Canada] ; Chunhai Hao [Canada] ; Miguel A. Cabrita [Canada] ; Mark F. Vickers [Canada] ; Stephen A. Baldwin [Royaume-Uni] ; James D. Young [Canada] ; Carol E. Cass [Canada]Source :
- Neuropharmacology [ 0028-3908 ] ; 2001.
Abstract
Nucleoside transport processes play an important role in human cells in salvage of nucleosides used in the biosynthesis of nucleic acids and in regulating endogenous adenosine concentrations in the human central nervous system (CNS). By altering the levels of adenosine available to interact with cell–surface receptors, nucleoside transporters have profound effects on the ability of adenosine to modulate neurotransmission, vascular tone and other physiological events. Although the human equilibrative nucleoside transporters 1 and 2 (hENT1 and hENT2) are believed to play a crucial role in modulating brain function, their distribution within the major divisions of the human CNS is not known. In this work, antibodies specific for hENT1 and hENT2 were produced against fragments of the transporter proteins and used for immunoblot analysis of enriched membrane fractions prepared from several regions of the human brain. While hENT1 was most prevalent in the frontal and parietal lobes of the cerebral cortex, thalamus, midbrain and basal ganglia, hENT2 was concentrated in the cerebellum and brainstem regions, particularly the pons. The apparent reciprocal distribution of hENT1 and hENT2 in human brain suggests that these nucleoside transporter proteins are produced in distinct regions of the CNS where they function in nucleoside salvage and/or regulation of exogenous adenosine. Within the brain regions that were investigated, the pattern of hENT1 distribution correlated well with adenosine A1 receptor abundance. The regional co-localization of hENT1 and A1 receptor protein suggests an important role of hENT1-mediated transport process in the control of neuromodulatory actions mediated by adenosine A1 receptors in human brain.
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DOI: 10.1016/S0028-3908(00)00207-0
Affiliations:
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Jennings</name><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Department of Oncology, University of Alberta, Edmonton, Alberta</wicri:regionArea><wicri:noRegion>Alberta</wicri:noRegion></affiliation></author><author><name sortKey="Hao, Chunhai" sort="Hao, Chunhai" uniqKey="Hao C" first="Chunhai" last="Hao">Chunhai Hao</name><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta</wicri:regionArea><wicri:noRegion>Alberta</wicri:noRegion></affiliation></author><author><name sortKey="Cabrita, Miguel A" sort="Cabrita, Miguel A" uniqKey="Cabrita M" first="Miguel A" last="Cabrita">Miguel A. Cabrita</name><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Department of Biochemistry, University of Alberta, Edmonton, Alberta</wicri:regionArea><wicri:noRegion>Alberta</wicri:noRegion></affiliation></author><author><name sortKey="Vickers, Mark F" sort="Vickers, Mark F" uniqKey="Vickers M" first="Mark F" last="Vickers">Mark F. Vickers</name><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Department of Biochemistry, University of Alberta, Edmonton, Alberta</wicri:regionArea><wicri:noRegion>Alberta</wicri:noRegion></affiliation></author><author><name sortKey="Baldwin, Stephen A" sort="Baldwin, Stephen A" uniqKey="Baldwin S" first="Stephen A" last="Baldwin">Stephen A. Baldwin</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="D Young, James" sort="D Young, James" uniqKey="D Young J" first="James" last="D. Young">James D. Young</name><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Department of Physiology, University of Alberta, Edmonton, Alberta</wicri:regionArea><wicri:noRegion>Alberta</wicri:noRegion></affiliation></author><author><name sortKey="Cass, Carol E" sort="Cass, Carol E" uniqKey="Cass C" first="Carol E" last="Cass">Carol E. Cass</name><affiliation wicri:level="1"><country wicri:rule="url">Canada</country></affiliation><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Department of Oncology, University of Alberta, Edmonton, Alberta</wicri:regionArea><wicri:noRegion>Alberta</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Neuropharmacology</title><title level="j" type="abbrev">NP</title><idno type="ISSN">0028-3908</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001">2001</date><biblScope unit="volume">40</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="722">722</biblScope><biblScope unit="page" to="731">731</biblScope></imprint><idno type="ISSN">0028-3908</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0028-3908</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Nucleoside transport processes play an important role in human cells in salvage of nucleosides used in the biosynthesis of nucleic acids and in regulating endogenous adenosine concentrations in the human central nervous system (CNS). By altering the levels of adenosine available to interact with cell–surface receptors, nucleoside transporters have profound effects on the ability of adenosine to modulate neurotransmission, vascular tone and other physiological events. Although the human equilibrative nucleoside transporters 1 and 2 (hENT1 and hENT2) are believed to play a crucial role in modulating brain function, their distribution within the major divisions of the human CNS is not known. In this work, antibodies specific for hENT1 and hENT2 were produced against fragments of the transporter proteins and used for immunoblot analysis of enriched membrane fractions prepared from several regions of the human brain. While hENT1 was most prevalent in the frontal and parietal lobes of the cerebral cortex, thalamus, midbrain and basal ganglia, hENT2 was concentrated in the cerebellum and brainstem regions, particularly the pons. The apparent reciprocal distribution of hENT1 and hENT2 in human brain suggests that these nucleoside transporter proteins are produced in distinct regions of the CNS where they function in nucleoside salvage and/or regulation of exogenous adenosine. Within the brain regions that were investigated, the pattern of hENT1 distribution correlated well with adenosine A1 receptor abundance. The regional co-localization of hENT1 and A1 receptor protein suggests an important role of hENT1-mediated transport process in the control of neuromodulatory actions mediated by adenosine A1 receptors in human brain.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Yorkshire-et-Humber</li></region><settlement><li>Leeds</li></settlement><orgName><li>Université de Leeds</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Jennings, Lori L" sort="Jennings, Lori L" uniqKey="Jennings L" first="Lori L" last="Jennings">Lori L. Jennings</name></noRegion><name sortKey="Cabrita, Miguel A" sort="Cabrita, Miguel A" uniqKey="Cabrita M" first="Miguel A" last="Cabrita">Miguel A. Cabrita</name><name sortKey="Cass, Carol E" sort="Cass, Carol E" uniqKey="Cass C" first="Carol E" last="Cass">Carol E. Cass</name><name sortKey="Cass, Carol E" sort="Cass, Carol E" uniqKey="Cass C" first="Carol E" last="Cass">Carol E. Cass</name><name sortKey="D Young, James" sort="D Young, James" uniqKey="D Young J" first="James" last="D. Young">James D. Young</name><name sortKey="Hao, Chunhai" sort="Hao, Chunhai" uniqKey="Hao C" first="Chunhai" last="Hao">Chunhai Hao</name><name sortKey="Vickers, Mark F" sort="Vickers, Mark F" uniqKey="Vickers M" first="Mark F" last="Vickers">Mark F. Vickers</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Baldwin, Stephen A" sort="Baldwin, Stephen A" uniqKey="Baldwin S" first="Stephen A" last="Baldwin">Stephen A. Baldwin</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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