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Control of Dopamine Signal in High-Order Receptor Complex on Striatal Astrocytes.

Sarah Amato1, Monica Averna2, Elisa Farsetti1

  • 1Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, Viale Cembrano 4, 16148 Genova, Italy.

International Journal of Molecular Sciences
|August 29, 2024
PubMed
Summary

G protein-coupled receptor (GPCR) interactions form novel signaling units. This study reveals a novel adenosine A2A-dopamine D2-oxytocin receptor complex in striatal astrocytes, modulating glutamate release and offering therapeutic targets.

Keywords:
adenosine receptorastrocyte processdopamine receptorglutamateheteromershigh-order receptor complexintracellular calciumneurogliaoxytocinreceptor mosaic

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Area of Science:

  • Neuroscience
  • Molecular Pharmacology
  • Cell Biology

Background:

  • G protein-coupled receptors (GPCRs) form receptor-receptor interactions (RRIs), creating distinct functional entities.
  • Heteromers of adenosine A2A (A2A), dopamine D2 (D2), and oxytocin receptors (OTR) exist, but their role in striatal astrocytes remains unexplored.

Purpose of the Study:

  • To investigate the existence of a high-order A2A-D2-OTR complex in striatal astrocytes.
  • To determine the role of this complex in modulating cytosolic calcium and glutamate release.

Main Methods:

  • Biophysical and functional assays were employed.
  • Imaging, biochemical, and bioinformatic approaches confirmed the complex's structure.

Main Results:

  • The A2A-D2-OTR complex exists and exhibits a ternary structure in astrocyte membranes.
  • OTR facilitates D2 signaling, while A2A inhibits D2 and OTR-mediated effects on D2.
  • D2 receptors are central to regulating astrocytic glutamate release.

Conclusions:

  • The A2A-D2-OTR heterotrimer integrates neurotransmitter signaling in the striatum.
  • This complex represents a potential selective pharmacological target for neuropsychiatric and neurodegenerative diseases.