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Identification of Dopamine D1–D3 Receptor Heteromers

Identifieur interne : 002182 ( Main/Exploration ); précédent : 002181; suivant : 002183

Identification of Dopamine D1–D3 Receptor Heteromers

Auteurs : Daniel Marcellino ; Sergi Ferré ; Vicent Casad ; Antonio Cortés ; Bernard Le Foll [Canada] ; Carmen Mazzola ; Filippo Drago ; Oliver Saur [Allemagne] ; Holger Stark [Allemagne] ; Aroa Soriano ; Chanel Barnes ; Steven R. Goldberg ; Carme Lluis ; Kjell Fuxe ; Rafael Franco

Source :

RBID : PMC:2533781

Abstract

The function of dopamine D3 receptors present in the striatum has remained elusive. In the present study evidence is provided for the existence of dopamine D1–D3 receptor heteromers and for an intramembrane D1–D3 receptor cross-talk in living cells and in the striatum. The formation of D1–D3 receptor heteromers was demonstrated by fluorescence resonance energy transfer and bioluminescence resonance energy transfer techniques in transfected mammalian cells. In membrane preparations from these cells, a synergistic D1–D3intramembrane receptor-receptor interaction was observed, by which D3 receptor stimulation enhances D1 receptor agonist affinity, indicating that the D1–D3 intramembrane receptor-receptor interaction is a biochemical characteristic of the D1–D3 receptor heteromer. The same biochemical characteristic was also observed in membrane preparations from brain striatum, demonstrating the striatal co-localization and heteromerization of D1 and D3 receptors. According to the synergistic D1–D3 intramembrane receptor-receptor interaction, experiments in reserpinized mice showed that D3 receptor stimulation potentiates D1 receptor-mediated behavioral effects by a different mechanism than D2 receptor stimulation. The present study shows that a main functional significance of the D3 receptor is to obtain a stronger dopaminergic response in the striatal neurons that co-express the two receptors.


Url:
DOI: 10.1074/jbc.M710349200
PubMed: 18644790
PubMed Central: 2533781


Affiliations:

Links toward previous steps (curation, corpus...)

Le document en format XML

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<div type="abstract" xml:lang="en">
<p>The function of dopamine D
<sub>3</sub>
receptors present in the striatum has remained elusive. In the present study evidence is provided for the existence of dopamine D
<sub>1</sub>
–D
<sub>3</sub>
receptor heteromers and for an intramembrane D
<sub>1</sub>
–D
<sub>3</sub>
receptor cross-talk in living cells and in the striatum. The formation of D
<sub>1</sub>
–D
<sub>3</sub>
receptor heteromers was demonstrated by fluorescence resonance energy transfer and bioluminescence resonance energy transfer techniques in transfected mammalian cells. In membrane preparations from these cells, a synergistic D
<sub>1</sub>
–D
<sub>3</sub>
intramembrane receptor-receptor interaction was observed, by which D
<sub>3</sub>
receptor stimulation enhances D
<sub>1</sub>
receptor agonist affinity, indicating that the D
<sub>1</sub>
–D
<sub>3</sub>
intramembrane receptor-receptor interaction is a biochemical characteristic of the D
<sub>1</sub>
–D
<sub>3</sub>
receptor heteromer. The same biochemical characteristic was also observed in membrane preparations from brain striatum, demonstrating the striatal co-localization and heteromerization of D
<sub>1</sub>
and D
<sub>3</sub>
receptors. According to the synergistic D
<sub>1</sub>
–D
<sub>3</sub>
intramembrane receptor-receptor interaction, experiments in reserpinized mice showed that D
<sub>3</sub>
receptor stimulation potentiates D
<sub>1</sub>
receptor-mediated behavioral effects by a different mechanism than D
<sub>2</sub>
receptor stimulation. The present study shows that a main functional significance of the D
<sub>3</sub>
receptor is to obtain a stronger dopaminergic response in the striatal neurons that co-express the two receptors.</p>
</div>
</front>
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<name sortKey="Fuxe, Kjell" sort="Fuxe, Kjell" uniqKey="Fuxe K" first="Kjell" last="Fuxe">Kjell Fuxe</name>
<name sortKey="Goldberg, Steven R" sort="Goldberg, Steven R" uniqKey="Goldberg S" first="Steven R." last="Goldberg">Steven R. Goldberg</name>
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<name sortKey="Marcellino, Daniel" sort="Marcellino, Daniel" uniqKey="Marcellino D" first="Daniel" last="Marcellino">Daniel Marcellino</name>
<name sortKey="Mazzola, Carmen" sort="Mazzola, Carmen" uniqKey="Mazzola C" first="Carmen" last="Mazzola">Carmen Mazzola</name>
<name sortKey="Soriano, Aroa" sort="Soriano, Aroa" uniqKey="Soriano A" first="Aroa" last="Soriano">Aroa Soriano</name>
</noCountry>
<country name="Canada">
<region name="Ontario">
<name sortKey="Le Foll, Bernard" sort="Le Foll, Bernard" uniqKey="Le Foll B" first="Bernard" last="Le Foll">Bernard Le Foll</name>
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</country>
<country name="Allemagne">
<region name="Hesse (Land)">
<name sortKey="Saur, Oliver" sort="Saur, Oliver" uniqKey="Saur O" first="Oliver" last="Saur">Oliver Saur</name>
</region>
<name sortKey="Stark, Holger" sort="Stark, Holger" uniqKey="Stark H" first="Holger" last="Stark">Holger Stark</name>
</country>
</tree>
</affiliations>
</record>

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