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  2. Receptor density influences ligand-induced dopamine D2L receptor homodimerization

Receptor density influences ligand-induced dopamine D2L receptor homodimerization

  • Eur J Pharmacol. 2021 Nov 15;911:174557. doi: 10.1016/j.ejphar.2021.174557.
Mattia Ferraiolo 1 Hicham Atik 1 Romane Ponthot 1 Inês Belo do Nascimento 1 Pauline Beckers 1 Christophe Stove 2 Emmanuel Hermans 3
Affiliations

Affiliations

  • 1 Neuropharmacology Laboratory, Institute of Neuroscience, UCLouvain, Brussels, Belgium.
  • 2 Laboratory of Toxicology, Department of Bioanalysis, Ghent University, Ghent, Belgium.
  • 3 Neuropharmacology Laboratory, Institute of Neuroscience, UCLouvain, Brussels, Belgium. Electronic address: emmanuel.hermans@uclouvain.be.
Abstract

Chronic treatments with dopamine D2 receptor ligands induce fluctuations in D2 receptor density. Since D2 receptors tend to assemble as homodimers, we hypothesized that receptor density might influence constitutive and ligand-induced homodimerization. Using a nanoluciferase-based complementation assay to monitor dopamine D2L receptor homodimerization in a cellular model enabling the tetracycline-controlled expression of dopamine D2L receptors, we observed that increasing receptor density promoted constitutive dopamine D2L receptor homodimerization. Receptor full agonists promoted homodimerization, while antagonists and partial agonists disrupted dopamine D2L receptor homodimers. High receptor densities enhanced this inhibitory effect only for receptor antagonists. Taken together, our findings indicate that both receptor density and receptor ligands influence dopamine D2L receptor homodimerization, albeit excluding any strict correlation with ligands' intrinsic activity and highlighting further complexity to dopaminergic pharmacology.

Keywords

Antiparkinsonian; Antipsychotic; D2L; Dimers; Dopamine; G protein coupled receptor; Luciferase; Oligomers; Parkinson's disease; Receptor density; Schizophrenia.

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