期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 283, 期 38, 页码 26016-26025出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M710349200
关键词
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资金
- National Institute on Drug Abuse
- Ministerio de Ciencia y Tecnologia [SAF2006-00170]
The function of dopamine D-3 receptors present in the striatum has remained elusive. In the present study evidence is provided for the existence of dopamine D-1-D-3 receptor heteromers and for an intramembrane D-1-D-3 receptor cross-talk in living cells and in the striatum. The formation of D-1-D-3 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-D-3 intramembrane receptor-receptor interaction was observed, by which D3 receptor stimulation enhances D-1 receptor agonist affinity, indicating that the D-1-D-3 intramembrane receptor-receptor interaction is a biochemical characteristic of the D-1-D-3 receptor heteromer. The same biochemical characteristic was also observed in membrane preparations from brain striatum, demonstrating the striatal co-localization and heteromerization of D-1 and D-3 receptors. According to the synergistic D-1-D-3 intramembrane receptor-receptor interaction, experiments in reserpinized mice showed that D-3 receptor stimulation potentiates D-1 receptor-mediated behavioral effects by a different mechanism than D-2 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.
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