Trans-Modulation of the Somatostatin Type 2A Receptor Trafficking by Insulin-Regulated Aminopeptidase Decreases Limbic Seizures.
Identifieur interne : 002A39 ( PubMed/Corpus ); précédent : 002A38; suivant : 002A40Trans-Modulation of the Somatostatin Type 2A Receptor Trafficking by Insulin-Regulated Aminopeptidase Decreases Limbic Seizures.
Auteurs : Dimitri De Bundel ; Assia Fafouri ; Zsolt Csaba ; Ellen Loyens ; Sophie Lebon ; Vincent El Ghouzzi ; Stéphane Peineau ; Guilan Vodjdani ; Foteini Kiagiadaki ; Najat Aourz ; Jessica Coppens ; Laura Walrave ; Jeanelle Portelli ; Patrick Vanderheyden ; Siew Yeen Chai ; Kyriaki Thermos ; Véronique Bernard ; Graham Collingridge ; Stéphane Auvin ; Pierre Gressens ; Ilse Smolders ; Pascal DournaudSource :
- The Journal of neuroscience : the official journal of the Society for Neuroscience [ 1529-2401 ] ; 2015.
English descriptors
- KwdEn :
- Animals, CHO Cells, Cricetinae, Cricetulus, Cystinyl Aminopeptidase (metabolism), Hippocampus (metabolism), Humans, Limbic System (metabolism), Male, Mice, Protein Transport (physiology), Rats, Rats, Wistar, Receptors, Somatostatin (metabolism), Seizures (metabolism), Seizures (prevention & control).
- MESH :
- chemical , metabolism : Cystinyl Aminopeptidase, Receptors, Somatostatin.
- metabolism : Hippocampus, Limbic System, Seizures.
- physiology : Protein Transport.
- prevention & control : Seizures.
- Animals, CHO Cells, Cricetinae, Cricetulus, Humans, Male, Mice, Rats, Rats, Wistar.
Abstract
Within the hippocampus, the major somatostatin (SRIF) receptor subtype, the sst2A receptor, is localized at postsynaptic sites of the principal neurons where it modulates neuronal activity. Following agonist exposure, this receptor rapidly internalizes and recycles slowly through the trans-Golgi network. In epilepsy, a high and chronic release of somatostatin occurs, which provokes, in both rat and human tissue, a decrease in the density of this inhibitory receptor at the cell surface. The insulin-regulated aminopeptidase (IRAP) is involved in vesicular trafficking and shares common regional distribution with the sst2A receptor. In addition, IRAP ligands display anticonvulsive properties. We therefore sought to assess by in vitro and in vivo experiments in hippocampal rat tissue whether IRAP ligands could regulate the trafficking of the sst2A receptor and, consequently, modulate limbic seizures. Using pharmacological and cell biological approaches, we demonstrate that IRAP ligands accelerate the recycling of the sst2A receptor that has internalized in neurons in vitro or in vivo. Most importantly, because IRAP ligands increase the density of this inhibitory receptor at the plasma membrane, they also potentiate the neuropeptide SRIF inhibitory effects on seizure activity. Our results further demonstrate that IRAP is a therapeutic target for the treatment of limbic seizures and possibly for other neurological conditions in which downregulation of G-protein-coupled receptors occurs.
DOI: 10.1523/JNEUROSCI.0476-15.2015
PubMed: 26311777
Links to Exploration step
pubmed:26311777Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Trans-Modulation of the Somatostatin Type 2A Receptor Trafficking by Insulin-Regulated Aminopeptidase Decreases Limbic Seizures.</title><author><name sortKey="De Bundel, Dimitri" sort="De Bundel, Dimitri" uniqKey="De Bundel D" first="Dimitri" last="De Bundel">Dimitri De Bundel</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Fafouri, Assia" sort="Fafouri, Assia" uniqKey="Fafouri A" first="Assia" last="Fafouri">Assia Fafouri</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Csaba, Zsolt" sort="Csaba, Zsolt" uniqKey="Csaba Z" first="Zsolt" last="Csaba">Zsolt Csaba</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Loyens, Ellen" sort="Loyens, Ellen" uniqKey="Loyens E" first="Ellen" last="Loyens">Ellen Loyens</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Lebon, Sophie" sort="Lebon, Sophie" uniqKey="Lebon S" first="Sophie" last="Lebon">Sophie Lebon</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="El Ghouzzi, Vincent" sort="El Ghouzzi, Vincent" uniqKey="El Ghouzzi V" first="Vincent" last="El Ghouzzi">Vincent El Ghouzzi</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Peineau, Stephane" sort="Peineau, Stephane" uniqKey="Peineau S" first="Stéphane" last="Peineau">Stéphane Peineau</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France, MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Vodjdani, Guilan" sort="Vodjdani, Guilan" uniqKey="Vodjdani G" first="Guilan" last="Vodjdani">Guilan Vodjdani</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kiagiadaki, Foteini" sort="Kiagiadaki, Foteini" uniqKey="Kiagiadaki F" first="Foteini" last="Kiagiadaki">Foteini Kiagiadaki</name><affiliation><nlm:affiliation>Laboratory of Pharmacology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Aourz, Najat" sort="Aourz, Najat" uniqKey="Aourz N" first="Najat" last="Aourz">Najat Aourz</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Coppens, Jessica" sort="Coppens, Jessica" uniqKey="Coppens J" first="Jessica" last="Coppens">Jessica Coppens</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Walrave, Laura" sort="Walrave, Laura" uniqKey="Walrave L" first="Laura" last="Walrave">Laura Walrave</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Portelli, Jeanelle" sort="Portelli, Jeanelle" uniqKey="Portelli J" first="Jeanelle" last="Portelli">Jeanelle Portelli</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Vanderheyden, Patrick" sort="Vanderheyden, Patrick" uniqKey="Vanderheyden P" first="Patrick" last="Vanderheyden">Patrick Vanderheyden</name><affiliation><nlm:affiliation>Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Chai, Siew Yeen" sort="Chai, Siew Yeen" uniqKey="Chai S" first="Siew Yeen" last="Chai">Siew Yeen Chai</name><affiliation><nlm:affiliation>Department of Physiology, Monash University, Victoria 3052, Australia, and.</nlm:affiliation></affiliation></author><author><name sortKey="Thermos, Kyriaki" sort="Thermos, Kyriaki" uniqKey="Thermos K" first="Kyriaki" last="Thermos">Kyriaki Thermos</name><affiliation><nlm:affiliation>Laboratory of Pharmacology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Bernard, Veronique" sort="Bernard, Veronique" uniqKey="Bernard V" first="Véronique" last="Bernard">Véronique Bernard</name><affiliation><nlm:affiliation>Inserm U952, CNRS UMR7224, Université Pierre et Marie Curie, 75005 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Collingridge, Graham" sort="Collingridge, Graham" uniqKey="Collingridge G" first="Graham" last="Collingridge">Graham Collingridge</name><affiliation><nlm:affiliation>MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Auvin, Stephane" sort="Auvin, Stephane" uniqKey="Auvin S" first="Stéphane" last="Auvin">Stéphane Auvin</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gressens, Pierre" sort="Gressens, Pierre" uniqKey="Gressens P" first="Pierre" last="Gressens">Pierre Gressens</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Smolders, Ilse" sort="Smolders, Ilse" uniqKey="Smolders I" first="Ilse" last="Smolders">Ilse Smolders</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Dournaud, Pascal" sort="Dournaud, Pascal" uniqKey="Dournaud P" first="Pascal" last="Dournaud">Pascal Dournaud</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France, pascal.dournaud@inserm.fr.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26311777</idno><idno type="pmid">26311777</idno><idno type="doi">10.1523/JNEUROSCI.0476-15.2015</idno><idno type="wicri:Area/PubMed/Corpus">002A39</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002A39</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Trans-Modulation of the Somatostatin Type 2A Receptor Trafficking by Insulin-Regulated Aminopeptidase Decreases Limbic Seizures.</title><author><name sortKey="De Bundel, Dimitri" sort="De Bundel, Dimitri" uniqKey="De Bundel D" first="Dimitri" last="De Bundel">Dimitri De Bundel</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Fafouri, Assia" sort="Fafouri, Assia" uniqKey="Fafouri A" first="Assia" last="Fafouri">Assia Fafouri</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Csaba, Zsolt" sort="Csaba, Zsolt" uniqKey="Csaba Z" first="Zsolt" last="Csaba">Zsolt Csaba</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Loyens, Ellen" sort="Loyens, Ellen" uniqKey="Loyens E" first="Ellen" last="Loyens">Ellen Loyens</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Lebon, Sophie" sort="Lebon, Sophie" uniqKey="Lebon S" first="Sophie" last="Lebon">Sophie Lebon</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="El Ghouzzi, Vincent" sort="El Ghouzzi, Vincent" uniqKey="El Ghouzzi V" first="Vincent" last="El Ghouzzi">Vincent El Ghouzzi</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Peineau, Stephane" sort="Peineau, Stephane" uniqKey="Peineau S" first="Stéphane" last="Peineau">Stéphane Peineau</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France, MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Vodjdani, Guilan" sort="Vodjdani, Guilan" uniqKey="Vodjdani G" first="Guilan" last="Vodjdani">Guilan Vodjdani</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kiagiadaki, Foteini" sort="Kiagiadaki, Foteini" uniqKey="Kiagiadaki F" first="Foteini" last="Kiagiadaki">Foteini Kiagiadaki</name><affiliation><nlm:affiliation>Laboratory of Pharmacology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Aourz, Najat" sort="Aourz, Najat" uniqKey="Aourz N" first="Najat" last="Aourz">Najat Aourz</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Coppens, Jessica" sort="Coppens, Jessica" uniqKey="Coppens J" first="Jessica" last="Coppens">Jessica Coppens</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Walrave, Laura" sort="Walrave, Laura" uniqKey="Walrave L" first="Laura" last="Walrave">Laura Walrave</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Portelli, Jeanelle" sort="Portelli, Jeanelle" uniqKey="Portelli J" first="Jeanelle" last="Portelli">Jeanelle Portelli</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Vanderheyden, Patrick" sort="Vanderheyden, Patrick" uniqKey="Vanderheyden P" first="Patrick" last="Vanderheyden">Patrick Vanderheyden</name><affiliation><nlm:affiliation>Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Chai, Siew Yeen" sort="Chai, Siew Yeen" uniqKey="Chai S" first="Siew Yeen" last="Chai">Siew Yeen Chai</name><affiliation><nlm:affiliation>Department of Physiology, Monash University, Victoria 3052, Australia, and.</nlm:affiliation></affiliation></author><author><name sortKey="Thermos, Kyriaki" sort="Thermos, Kyriaki" uniqKey="Thermos K" first="Kyriaki" last="Thermos">Kyriaki Thermos</name><affiliation><nlm:affiliation>Laboratory of Pharmacology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Bernard, Veronique" sort="Bernard, Veronique" uniqKey="Bernard V" first="Véronique" last="Bernard">Véronique Bernard</name><affiliation><nlm:affiliation>Inserm U952, CNRS UMR7224, Université Pierre et Marie Curie, 75005 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Collingridge, Graham" sort="Collingridge, Graham" uniqKey="Collingridge G" first="Graham" last="Collingridge">Graham Collingridge</name><affiliation><nlm:affiliation>MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Auvin, Stephane" sort="Auvin, Stephane" uniqKey="Auvin S" first="Stéphane" last="Auvin">Stéphane Auvin</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gressens, Pierre" sort="Gressens, Pierre" uniqKey="Gressens P" first="Pierre" last="Gressens">Pierre Gressens</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Smolders, Ilse" sort="Smolders, Ilse" uniqKey="Smolders I" first="Ilse" last="Smolders">Ilse Smolders</name><affiliation><nlm:affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Dournaud, Pascal" sort="Dournaud, Pascal" uniqKey="Dournaud P" first="Pascal" last="Dournaud">Pascal Dournaud</name><affiliation><nlm:affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France, pascal.dournaud@inserm.fr.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The Journal of neuroscience : the official journal of the Society for Neuroscience</title><idno type="eISSN">1529-2401</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>CHO Cells</term><term>Cricetinae</term><term>Cricetulus</term><term>Cystinyl Aminopeptidase (metabolism)</term><term>Hippocampus (metabolism)</term><term>Humans</term><term>Limbic System (metabolism)</term><term>Male</term><term>Mice</term><term>Protein Transport (physiology)</term><term>Rats</term><term>Rats, Wistar</term><term>Receptors, Somatostatin (metabolism)</term><term>Seizures (metabolism)</term><term>Seizures (prevention & control)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cystinyl Aminopeptidase</term><term>Receptors, Somatostatin</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Hippocampus</term><term>Limbic System</term><term>Seizures</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Protein Transport</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Seizures</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>CHO Cells</term><term>Cricetinae</term><term>Cricetulus</term><term>Humans</term><term>Male</term><term>Mice</term><term>Rats</term><term>Rats, Wistar</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Within the hippocampus, the major somatostatin (SRIF) receptor subtype, the sst2A receptor, is localized at postsynaptic sites of the principal neurons where it modulates neuronal activity. Following agonist exposure, this receptor rapidly internalizes and recycles slowly through the trans-Golgi network. In epilepsy, a high and chronic release of somatostatin occurs, which provokes, in both rat and human tissue, a decrease in the density of this inhibitory receptor at the cell surface. The insulin-regulated aminopeptidase (IRAP) is involved in vesicular trafficking and shares common regional distribution with the sst2A receptor. In addition, IRAP ligands display anticonvulsive properties. We therefore sought to assess by in vitro and in vivo experiments in hippocampal rat tissue whether IRAP ligands could regulate the trafficking of the sst2A receptor and, consequently, modulate limbic seizures. Using pharmacological and cell biological approaches, we demonstrate that IRAP ligands accelerate the recycling of the sst2A receptor that has internalized in neurons in vitro or in vivo. Most importantly, because IRAP ligands increase the density of this inhibitory receptor at the plasma membrane, they also potentiate the neuropeptide SRIF inhibitory effects on seizure activity. Our results further demonstrate that IRAP is a therapeutic target for the treatment of limbic seizures and possibly for other neurological conditions in which downregulation of G-protein-coupled receptors occurs.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26311777</PMID><DateCreated><Year>2015</Year><Month>08</Month><Day>28</Day></DateCreated><DateCompleted><Year>2015</Year><Month>11</Month><Day>24</Day></DateCompleted><DateRevised><Year>2017</Year><Month>11</Month><Day>10</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1529-2401</ISSN><JournalIssue CitedMedium="Internet"><Volume>35</Volume><Issue>34</Issue><PubDate><Year>2015</Year><Month>Aug</Month><Day>26</Day></PubDate></JournalIssue><Title>The Journal of neuroscience : the official journal of the Society for Neuroscience</Title><ISOAbbreviation>J. Neurosci.</ISOAbbreviation></Journal><ArticleTitle>Trans-Modulation of the Somatostatin Type 2A Receptor Trafficking by Insulin-Regulated Aminopeptidase Decreases Limbic Seizures.</ArticleTitle><Pagination><MedlinePgn>11960-75</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1523/JNEUROSCI.0476-15.2015</ELocationID><Abstract><AbstractText Label="UNLABELLED">Within the hippocampus, the major somatostatin (SRIF) receptor subtype, the sst2A receptor, is localized at postsynaptic sites of the principal neurons where it modulates neuronal activity. Following agonist exposure, this receptor rapidly internalizes and recycles slowly through the trans-Golgi network. In epilepsy, a high and chronic release of somatostatin occurs, which provokes, in both rat and human tissue, a decrease in the density of this inhibitory receptor at the cell surface. The insulin-regulated aminopeptidase (IRAP) is involved in vesicular trafficking and shares common regional distribution with the sst2A receptor. In addition, IRAP ligands display anticonvulsive properties. We therefore sought to assess by in vitro and in vivo experiments in hippocampal rat tissue whether IRAP ligands could regulate the trafficking of the sst2A receptor and, consequently, modulate limbic seizures. Using pharmacological and cell biological approaches, we demonstrate that IRAP ligands accelerate the recycling of the sst2A receptor that has internalized in neurons in vitro or in vivo. Most importantly, because IRAP ligands increase the density of this inhibitory receptor at the plasma membrane, they also potentiate the neuropeptide SRIF inhibitory effects on seizure activity. Our results further demonstrate that IRAP is a therapeutic target for the treatment of limbic seizures and possibly for other neurological conditions in which downregulation of G-protein-coupled receptors occurs.</AbstractText><AbstractText Label="SIGNIFICANCE STATEMENT" NlmCategory="UNASSIGNED">The somatostatin type 2A receptor (sst2A) is localized on principal hippocampal neurons and displays anticonvulsant properties. Following agonist exposure, however, this receptor rapidly internalizes and recycles slowly. The insulin-regulated aminopeptidase (IRAP) is involved in vesicular trafficking and shares common regional distribution with the sst2A receptor. We therefore assessed by in vitro and in vivo experiments whether IRAP could regulate the trafficking of this receptor. We demonstrate that IRAP ligands accelerate sst2A recycling in hippocampal neurons. Because IRAP ligands increase the density of sst2A receptors at the plasma membrane, they also potentiate the effects of this inhibitory receptor on seizure activity. Our results further demonstrate that IRAP is a therapeutic target for the treatment of limbic seizures.</AbstractText><CopyrightInformation>Copyright © 2015 the authors 0270-6474/15/3511961-16$15.00/0.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>De Bundel</LastName><ForeName>Dimitri</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fafouri</LastName><ForeName>Assia</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Csaba</LastName><ForeName>Zsolt</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Loyens</LastName><ForeName>Ellen</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lebon</LastName><ForeName>Sophie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El Ghouzzi</LastName><ForeName>Vincent</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peineau</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France, MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vodjdani</LastName><ForeName>Guilan</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kiagiadaki</LastName><ForeName>Foteini</ForeName><Initials>F</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-3769-3149</Identifier><AffiliationInfo><Affiliation>Laboratory of Pharmacology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aourz</LastName><ForeName>Najat</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coppens</LastName><ForeName>Jessica</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Walrave</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Portelli</LastName><ForeName>Jeanelle</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vanderheyden</LastName><ForeName>Patrick</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Siew Yeen</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Department of Physiology, Monash University, Victoria 3052, Australia, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thermos</LastName><ForeName>Kyriaki</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Laboratory of Pharmacology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bernard</LastName><ForeName>Véronique</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Inserm U952, CNRS UMR7224, Université Pierre et Marie Curie, 75005 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Collingridge</LastName><ForeName>Graham</ForeName><Initials>G</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-9572-5359</Identifier><AffiliationInfo><Affiliation>MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Auvin</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gressens</LastName><ForeName>Pierre</ForeName><Initials>P</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-0909-4221</Identifier><AffiliationInfo><Affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smolders</LastName><ForeName>Ilse</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dournaud</LastName><ForeName>Pascal</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Inserm, U1141, 75019 Paris, France, University Paris Diderot, Sorbonne Paris Cité, UMR1141, 75019 Paris, France, pascal.dournaud@inserm.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MR/K023098/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Neurosci</MedlineTA><NlmUniqueID>8102140</NlmUniqueID><ISSNLinking>0270-6474</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017481">Receptors, Somatostatin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C106140">somatostatin receptor sst2A</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.11.3</RegistryNumber><NameOfSubstance UI="D010122">Cystinyl Aminopeptidase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.11.3</RegistryNumber><NameOfSubstance UI="C105964">leucyl-cystinyl aminopeptidase</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016466" MajorTopicYN="N">CHO Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006224" MajorTopicYN="N">Cricetinae</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003412" MajorTopicYN="N">Cricetulus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010122" MajorTopicYN="N">Cystinyl Aminopeptidase</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006624" MajorTopicYN="N">Hippocampus</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008032" MajorTopicYN="N">Limbic System</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D021381" MajorTopicYN="N">Protein Transport</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017208" MajorTopicYN="N">Rats, Wistar</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017481" MajorTopicYN="N">Receptors, Somatostatin</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012640" MajorTopicYN="N">Seizures</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">GPCR</Keyword><Keyword MajorTopicYN="N">insulin-regulated aminopeptidase</Keyword><Keyword MajorTopicYN="N">limbic seizures</Keyword><Keyword MajorTopicYN="N">neuropeptide</Keyword><Keyword MajorTopicYN="N">somatostatin</Keyword><Keyword MajorTopicYN="N">traffic</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>8</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>8</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>12</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26311777</ArticleId><ArticleId IdType="pii">35/34/11960</ArticleId><ArticleId IdType="doi">10.1523/JNEUROSCI.0476-15.2015</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002A39 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 002A39 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= PubMed
|étape= Corpus
|type= RBID
|clé= pubmed:26311777
|texte= Trans-Modulation of the Somatostatin Type 2A Receptor Trafficking by Insulin-Regulated Aminopeptidase Decreases Limbic Seizures.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:26311777" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |