Levodopa but not ropinirole induces an internalization of D1 dopamine receptors in parkinsonian rats
Identifieur interne : 004406 ( Main/Exploration ); précédent : 004405; suivant : 004407Levodopa but not ropinirole induces an internalization of D1 dopamine receptors in parkinsonian rats
Auteurs : Marie-Paule Muriel [France] ; Gaël Orieux [France] ; Etienne C. Hirsch [France]Source :
- Movement Disorders [ 0885-3185 ] ; 2002-11.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- Agonist, Animal, Animal model, Animals, Antiparkinson Agents (pharmacology), Antiparkinson agent, Carbidopa (pharmacology), Chemotherapy, Corpus Striatum (drug effects), Corpus Striatum (pathology), Cytoplasm (drug effects), Cytoplasm (pathology), D1 Dopamine receptor, D1 dopamine receptor, Drug Combinations, Immunohistochemistry, Indoles (pharmacology), Internalization, Levodopa, Levodopa (pharmacology), Male, Microscopy, Immunoelectron, Neurons (drug effects), Neurons (pathology), Oxidopamine, Parkinson disease, Parkinsonian Disorders (chemically induced), Parkinsonian Disorders (pathology), Rat, Rats, Rats, Sprague-Dawley, Receptors, Dopamine D1 (drug effects), Ropinirole, Synaptic Membranes (drug effects), Synaptic Membranes (pathology), Treatment, Tyrosine 3-Monooxygenase (metabolism), internalization, levodopa, parkinsonian rats, ropinirole.
- MESH :
- chemical , drug effects : Receptors, Dopamine D1.
- chemical , metabolism : Tyrosine 3-Monooxygenase.
- chemical , pharmacology : Antiparkinson Agents, Carbidopa, Indoles, Levodopa.
- chemically induced : Parkinsonian Disorders.
- drug effects : Corpus Striatum, Cytoplasm, Neurons, Synaptic Membranes.
- pathology : Corpus Striatum, Cytoplasm, Neurons, Parkinsonian Disorders, Synaptic Membranes.
- Animals, Drug Combinations, Male, Microscopy, Immunoelectron, Oxidopamine, Rats, Rats, Sprague-Dawley.
Abstract
Levodopa therapy in Parkinson's disease is mediated by dopamine receptors and, in a recent study, we showed that a Dl full agonist can induce an internalization of D1 dopamine receptors. The aim of the present study was to determine whether levodopa or a dopamine agonist such as ropinirole can also induce the internalization of D1 dopamine receptors in the striatum of control and hemiparkinsonian rats. The distribution of D1 dopamine receptors was analyzed by immunohistochemistry using a specific antibody. In control animals and 6‐hydroxydopamine (6‐OHDA)‐lesioned animals treated with saline, D1 dopamine receptors were localized at the level of the plasma membrane. In contrast, in both lesioned and nonlesioned animals receiving a single dose of levodopa, but not in animals receiving ropinirole, D1 dopamine receptors were internalized in the cytoplasm. This result is likely explained by the fact that ropinirole binds to non‐D1 dopamine receptors, whereas levodopa, which increases dopamine levels, indirectly acts on both D1 and D2 receptors. Ropinirole is consequently less likely to desensitize D1 dopamine receptors than levodopa and, thus, to reduce the efficacy of the treatment. © 2002 Movement Disorder Society
Url:
DOI: 10.1002/mds.10256
Affiliations:
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Le document en format XML
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<term>Antiparkinson Agents (pharmacology)</term>
<term>Antiparkinson agent</term>
<term>Carbidopa (pharmacology)</term>
<term>Chemotherapy</term>
<term>Corpus Striatum (drug effects)</term>
<term>Corpus Striatum (pathology)</term>
<term>Cytoplasm (drug effects)</term>
<term>Cytoplasm (pathology)</term>
<term>D1 Dopamine receptor</term>
<term>D1 dopamine receptor</term>
<term>Drug Combinations</term>
<term>Immunohistochemistry</term>
<term>Indoles (pharmacology)</term>
<term>Internalization</term>
<term>Levodopa</term>
<term>Levodopa (pharmacology)</term>
<term>Male</term>
<term>Microscopy, Immunoelectron</term>
<term>Neurons (drug effects)</term>
<term>Neurons (pathology)</term>
<term>Oxidopamine</term>
<term>Parkinson disease</term>
<term>Parkinsonian Disorders (chemically induced)</term>
<term>Parkinsonian Disorders (pathology)</term>
<term>Rat</term>
<term>Rats</term>
<term>Rats, Sprague-Dawley</term>
<term>Receptors, Dopamine D1 (drug effects)</term>
<term>Ropinirole</term>
<term>Synaptic Membranes (drug effects)</term>
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<term>Treatment</term>
<term>Tyrosine 3-Monooxygenase (metabolism)</term>
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<term>Carbidopa</term>
<term>Indoles</term>
<term>Levodopa</term>
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<term>Cytoplasm</term>
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<term>Synaptic Membranes</term>
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<term>Drug Combinations</term>
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<front><div type="abstract" xml:lang="en">Levodopa therapy in Parkinson's disease is mediated by dopamine receptors and, in a recent study, we showed that a Dl full agonist can induce an internalization of D1 dopamine receptors. The aim of the present study was to determine whether levodopa or a dopamine agonist such as ropinirole can also induce the internalization of D1 dopamine receptors in the striatum of control and hemiparkinsonian rats. The distribution of D1 dopamine receptors was analyzed by immunohistochemistry using a specific antibody. In control animals and 6‐hydroxydopamine (6‐OHDA)‐lesioned animals treated with saline, D1 dopamine receptors were localized at the level of the plasma membrane. In contrast, in both lesioned and nonlesioned animals receiving a single dose of levodopa, but not in animals receiving ropinirole, D1 dopamine receptors were internalized in the cytoplasm. This result is likely explained by the fact that ropinirole binds to non‐D1 dopamine receptors, whereas levodopa, which increases dopamine levels, indirectly acts on both D1 and D2 receptors. Ropinirole is consequently less likely to desensitize D1 dopamine receptors than levodopa and, thus, to reduce the efficacy of the treatment. © 2002 Movement Disorder Society</div>
</front>
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