GAEAA receptor complex function in frontal cortex membranes from control and neurological patients
Identifieur interne : 000296 ( France/Analysis ); précédent : 000295; suivant : 000297GAEAA receptor complex function in frontal cortex membranes from control and neurological patients
Auteurs : G. Kenneth Lloyd [France] ; Armand Lowenthal [Belgique] ; France Javoy-Agid [France] ; Jean Constantidinis [Suisse]Source :
- European Journal of Pharmacology [ 0014-2999 ] ; 1991.
Abstract
The functional integrity of the GABAA receptof-benzodiazepine (BZ) recognition site-Cl− ionophore complex was assessed by means of [35S]TBPS (t-butylbicyclophosphorothionate) binding to frontal cortex membranes prepared from frozen postmortem brain tissue taken from control (n = 4), Alzheimer (n = 7), Parkinson (n = 3) and Huntington's chorea (n = 2) patients. Specific [35S]TBPS binding was similar in control, Parkinson's disease and Huntington's chorea brains, but was significantly reduced (78% control, P < 0.01) in frontal cortex membranes from Alzheimer's patients. The linkage between the BZ recognition sites and the GABAA receptor-linked Cl− ionophore was functionally intact in these membranes as BZ site agonists (zolpidem, alpidem, flunitrazepam and clonazepam) enhanced [35S]TBPS binding under the conditions used (well-washed membranes in the presence of 1.0 M NaCl). Zolpidem (BZ1 selective) exhibited a biphasic enhancement in control membranes whereas the other compounds induced a bell-shaped concentration-response curve. The enhancement of [35S]TBPS binding by alpidem, flunitrazepam and clonazepam was greater in frontal cortex membranes from Alzheimer's patients than in controls whereas it tended to be reduced in membranes from the brains of Huntington's chorea patients. These studies demonstrate the functional integrity of the GABAA receptor macromolecular complex and also the usefulness of [35S]TBPS binding in the study of human postmortem tissue.
Url:
DOI: 10.1016/0014-2999(91)90361-S
Affiliations:
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Kenneth Lloyd</name></author><author><name sortKey="Lowenthal, Armand" sort="Lowenthal, Armand" uniqKey="Lowenthal A" first="Armand" last="Lowenthal">Armand Lowenthal</name></author><author><name sortKey="Javoy Agid, France" sort="Javoy Agid, France" uniqKey="Javoy Agid F" first="France" last="Javoy-Agid">France Javoy-Agid</name></author><author><name sortKey="Constantidinis, Jean" sort="Constantidinis, Jean" uniqKey="Constantidinis J" first="Jean" last="Constantidinis">Jean Constantidinis</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:0A9C64FDFDDE488FB659612ABFEB2E432F72039D</idno><date when="1991" year="1991">1991</date><idno type="doi">10.1016/0014-2999(91)90361-S</idno><idno type="url">https://api.istex.fr/document/0A9C64FDFDDE488FB659612ABFEB2E432F72039D/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002B32</idno><idno type="wicri:Area/Main/Curation">002767</idno><idno type="wicri:Area/Main/Exploration">002667</idno><idno type="wicri:Area/France/Extraction">000296</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">GAEAA receptor complex function in frontal cortex membranes from control and neurological patients</title><author><name sortKey="Lloyd, G Kenneth" sort="Lloyd, G Kenneth" uniqKey="Lloyd G" first="G. 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Kenneth Lloyd</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Synlhélabo Recherche (L.E.R.S.), 58 Rue de la Glaciere, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lowenthal, Armand" sort="Lowenthal, Armand" uniqKey="Lowenthal A" first="Armand" last="Lowenthal">Armand Lowenthal</name><affiliation wicri:level="3"><country xml:lang="fr">Belgique</country><wicri:regionArea>Algemeen Ziekenhuis Middleheim, 2020 Antwerpen</wicri:regionArea><placeName><region type="province" nuts="2">Province d'Anvers</region><settlement type="city">Anvers</settlement></placeName></affiliation></author><author><name sortKey="Javoy Agid, France" sort="Javoy Agid, France" uniqKey="Javoy Agid F" first="France" last="Javoy-Agid">France Javoy-Agid</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Hopital Pitié Salpêtrière, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Constantidinis, Jean" sort="Constantidinis, Jean" uniqKey="Constantidinis J" first="Jean" last="Constantidinis">Jean Constantidinis</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Institutions Universitaires de Psychiatrie Genève (IUPG), 1225 Chène Bourg, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Pharmacology</title><title level="j" type="abbrev">EJP</title><idno type="ISSN">0014-2999</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1991">1991</date><biblScope unit="volume">197</biblScope><biblScope unit="issue">1–2</biblScope><biblScope unit="page" from="33">33</biblScope><biblScope unit="page" to="39">39</biblScope></imprint><idno type="ISSN">0014-2999</idno></series><idno type="istex">0A9C64FDFDDE488FB659612ABFEB2E432F72039D</idno><idno type="DOI">10.1016/0014-2999(91)90361-S</idno><idno type="PII">0014-2999(91)90361-S</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0014-2999</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The functional integrity of the GABAA receptof-benzodiazepine (BZ) recognition site-Cl− ionophore complex was assessed by means of [35S]TBPS (t-butylbicyclophosphorothionate) binding to frontal cortex membranes prepared from frozen postmortem brain tissue taken from control (n = 4), Alzheimer (n = 7), Parkinson (n = 3) and Huntington's chorea (n = 2) patients. Specific [35S]TBPS binding was similar in control, Parkinson's disease and Huntington's chorea brains, but was significantly reduced (78% control, P < 0.01) in frontal cortex membranes from Alzheimer's patients. The linkage between the BZ recognition sites and the GABAA receptor-linked Cl− ionophore was functionally intact in these membranes as BZ site agonists (zolpidem, alpidem, flunitrazepam and clonazepam) enhanced [35S]TBPS binding under the conditions used (well-washed membranes in the presence of 1.0 M NaCl). Zolpidem (BZ1 selective) exhibited a biphasic enhancement in control membranes whereas the other compounds induced a bell-shaped concentration-response curve. The enhancement of [35S]TBPS binding by alpidem, flunitrazepam and clonazepam was greater in frontal cortex membranes from Alzheimer's patients than in controls whereas it tended to be reduced in membranes from the brains of Huntington's chorea patients. These studies demonstrate the functional integrity of the GABAA receptor macromolecular complex and also the usefulness of [35S]TBPS binding in the study of human postmortem tissue.</div></front></TEI><affiliations><list><country><li>Belgique</li><li>France</li><li>Suisse</li></country><region><li>Province d'Anvers</li><li>Île-de-France</li></region><settlement><li>Anvers</li><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Lloyd, G Kenneth" sort="Lloyd, G Kenneth" uniqKey="Lloyd G" first="G. Kenneth" last="Lloyd">G. 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