Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa‐induced motor complications
Identifieur interne : 004160 ( Main/Exploration ); précédent : 004159; suivant : 004161Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa‐induced motor complications
Auteurs : Frédéric Calon [Canada] ; Marc Morissette [Canada] ; Ali H. Rajput [Canada] ; Oleh Hornykiewicz [Canada, Autriche] ; Paul J. Bédard [Canada] ; Thérèse Di Paolo [Canada]Source :
- Movement Disorders [ 0885-3185 ] ; 2003-03.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Antiparkinson Agents (adverse effects), Antiparkinson Agents (therapeutic use), Antiparkinson agent, Autoradiography, Biological transport, Brain (metabolism), Case-Control Studies, Catecholamine, Chemotherapy, Dopamine, Dopamine (metabolism), Dyskinesia, Dyskinesia, Drug-Induced (metabolism), Dyskinesia, Drug-Induced (physiopathology), Female, Gabaergic receptor, Globus Pallidus (metabolism), Human, Humans, Levodopa, Levodopa (adverse effects), Levodopa (therapeutic use), Male, Mechanism of action, Metabolism, Parkinson Disease (drug therapy), Parkinson Disease (metabolism), Parkinson disease, Postmortem Changes, Receptors, GABA (metabolism), Receptors, GABA-A (metabolism), Receptors, GABA-B (metabolism), Toxicity, Treatment, catecholamine, dyskinesias, globus pallidus, indolamine, levodopa, wearing‐off.
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- chemical , metabolism : Dopamine, Receptors, GABA, Receptors, GABA-A, Receptors, GABA-B.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- drug therapy : Parkinson Disease.
- metabolism : Brain, Dyskinesia, Drug-Induced, Globus Pallidus, Parkinson Disease.
- physiopathology : Dyskinesia, Drug-Induced.
- Aged, Aged, 80 and over, Autoradiography, Case-Control Studies, Female, Humans, Male, Postmortem Changes.
Abstract
Brain samples from 14 Parkinson's disease patients, 10 of whom developed motor complications (dyskinesias and/or wearing‐off) on dopaminomimetic therapy, and 11 controls were analyzed. Striatal 3β‐(4‐125I‐iodophenyl)tropane‐2β‐carboxylic acid isopropyl ester ([125I]RTI‐121) ‐specific binding to dopamine transporter and concentration of dopamine were markedly decreased, but no association between level of denervation and development of motor complications was observed. The homovanillic acid/dopamine ratio of concentrations was higher in putamen of patients with wearing‐off compared to those without. Striatal 35S‐labeled t‐butylbicyclophosphorothionate ([35S]TBPS) and [3H]flunitrazepam binding to GABAA receptors were unchanged in patients with Parkinson's disease, whereas [125I]CGP 64213 ‐specific binding to GABAB receptors was decreased in the putamen and external segment of the globus pallidus of parkinsonian patients compared with controls. [3H]Flunitrazepam binding was increased in the putamen of patients with wearing‐off compared to those without. [35S]TBPS–specific binding was increased in the ventral internal globus pallidus of dyskinetic subjects. These data suggest altered dopamine metabolism and increased GABAA receptors in the putamen related to the pathophysiology of wearing‐off. The present results also suggest that an up‐regulation of GABAA receptors in the internal globus pallidus is linked to the pathogenesis of levodopa‐induced dyskinesias. © 2002 Movement Disorder Society
Url:
DOI: 10.1002/mds.10343
Affiliations:
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Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>New York</pubPlace><date type="published" when="2003-03">2003-03</date><biblScope unit="vol">18</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="241">241</biblScope><biblScope unit="page" to="253">253</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">CD51CD78D35187E110BECD61BC009C5CEB097B2C</idno><idno type="DOI">10.1002/mds.10343</idno><idno type="ArticleID">MDS10343</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Antiparkinson agent</term><term>Autoradiography</term><term>Biological transport</term><term>Brain (metabolism)</term><term>Case-Control Studies</term><term>Catecholamine</term><term>Chemotherapy</term><term>Dopamine</term><term>Dopamine (metabolism)</term><term>Dyskinesia</term><term>Dyskinesia, Drug-Induced (metabolism)</term><term>Dyskinesia, Drug-Induced (physiopathology)</term><term>Female</term><term>Gabaergic receptor</term><term>Globus Pallidus (metabolism)</term><term>Human</term><term>Humans</term><term>Levodopa</term><term>Levodopa (adverse effects)</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Mechanism of action</term><term>Metabolism</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson disease</term><term>Postmortem Changes</term><term>Receptors, GABA (metabolism)</term><term>Receptors, GABA-A (metabolism)</term><term>Receptors, GABA-B (metabolism)</term><term>Toxicity</term><term>Treatment</term><term>catecholamine</term><term>dyskinesias</term><term>globus pallidus</term><term>indolamine</term><term>levodopa</term><term>wearing‐off</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term><term>Receptors, GABA</term><term>Receptors, GABA-A</term><term>Receptors, GABA-B</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Dyskinesia, Drug-Induced</term><term>Globus Pallidus</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Autoradiography</term><term>Case-Control Studies</term><term>Female</term><term>Humans</term><term>Male</term><term>Postmortem Changes</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Antiparkinsonien</term><term>Autoradiographie</term><term>Catécholamine</term><term>Chimiothérapie</term><term>Dopamine</term><term>Dyskinésie</term><term>Homme</term><term>Lévodopa</term><term>Mécanisme action</term><term>Métabolisme</term><term>Parkinson maladie</term><term>Récepteur gabaergique</term><term>Toxicité</term><term>Traitement</term><term>Transport biologique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Brain samples from 14 Parkinson's disease patients, 10 of whom developed motor complications (dyskinesias and/or wearing‐off) on dopaminomimetic therapy, and 11 controls were analyzed. Striatal 3β‐(4‐125I‐iodophenyl)tropane‐2β‐carboxylic acid isopropyl ester ([125I]RTI‐121) ‐specific binding to dopamine transporter and concentration of dopamine were markedly decreased, but no association between level of denervation and development of motor complications was observed. The homovanillic acid/dopamine ratio of concentrations was higher in putamen of patients with wearing‐off compared to those without. Striatal 35S‐labeled t‐butylbicyclophosphorothionate ([35S]TBPS) and [3H]flunitrazepam binding to GABAA receptors were unchanged in patients with Parkinson's disease, whereas [125I]CGP 64213 ‐specific binding to GABAB receptors was decreased in the putamen and external segment of the globus pallidus of parkinsonian patients compared with controls. [3H]Flunitrazepam binding was increased in the putamen of patients with wearing‐off compared to those without. [35S]TBPS–specific binding was increased in the ventral internal globus pallidus of dyskinetic subjects. These data suggest altered dopamine metabolism and increased GABAA receptors in the putamen related to the pathophysiology of wearing‐off. The present results also suggest that an up‐regulation of GABAA receptors in the internal globus pallidus is linked to the pathogenesis of levodopa‐induced dyskinesias. © 2002 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Autriche</li><li>Canada</li></country><region><li>Vienne (Autriche)</li></region><settlement><li>Vienne (Autriche)</li></settlement></list><tree><country name="Canada"><noRegion><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name></noRegion><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bédard">Paul J. Bédard</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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