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Receptor density influences ligand-induced dopamine D2L receptor homodimerization
Mattia Ferraiolo1, Hicham Atik1, Romane Ponthot1
1Neuropharmacology Laboratory, Institute of Neuroscience, UCLouvain, Brussels, Belgium.
European Journal of Pharmacology
|October 9, 2021
Summary
Dopamine D2 receptor density influences receptor homodimerization. Higher densities promote constitutive homodimerization and enhance antagonist disruption, adding complexity to dopaminergic pharmacology.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Chronic dopamine D2 receptor ligand treatment alters receptor density.
- Dopamine D2 receptors are known to form homodimers.
Purpose of the Study:
- To investigate the influence of dopamine D2 receptor density on receptor homodimerization.
- To determine how receptor density affects constitutive and ligand-induced homodimerization.
Main Methods:
- Utilized a nanoluciferase-based complementation assay.
- Employed a cellular model with tetracycline-controlled dopamine D2L receptor expression.
Main Results:
- Increased dopamine D2L receptor density promoted constitutive homodimerization.
- Full agonists enhanced homodimerization; antagonists and partial agonists disrupted it.
- High receptor densities amplified the inhibitory effect of antagonists.
Conclusions:
- Receptor density and ligand type both modulate dopamine D2L receptor homodimerization.
- The relationship between density, ligands, and homodimerization is complex and not strictly correlated with ligand intrinsic activity.
- Findings reveal new insights into dopaminergic system complexity.
Keywords:
AntiparkinsonianAntipsychoticD2LDimersDopamineG protein coupled receptorLuciferaseOligomersParkinson's diseaseReceptor densitySchizophreniaMore Related Videos
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