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 D 1-D3 intramembrane 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-D 3 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.
CITATION STYLE
Marcellino, D., Ferré, S., Casadó, V., Cortés, A., Le Foll, B., Mazzola, C., … Franco, R. (2008). Identification of Dopamine D1–D3 Receptor Heteromers. Journal of Biological Chemistry, 283(38), 26016–26025. https://doi.org/10.1074/jbc.m710349200
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