Receptor density influences the recruitment bias of aripiprazole and brexpiprazole at the dopamine D receptor.

Aripiprazole, brexpiprazole, and cariprazine are dopamine D receptor ligands considered as effective and tolerable antipsychotics. Brain imaging studies showed that schizophrenia is characterized by elevated dopamine receptor density, which is exacerbated by antipsychotic treatments. Despite the complexity of translating in vitro studies to human neurobiology, overexpression experiments in transfected cells provide a proof-of-concept model of the influence of receptor density on antipsychotic treatments.

Dopamine DL receptor density influences the recruitment of β-arrestin2 and G1 induced by antiparkinsonian drugs.

Introduction: Brain imaging studies have highlighted that the density of dopamine D receptors markedly fluctuates across the stages of Parkinson's disease and in response to pharmacological treatment. Moreover, receptor density constitutes a molecular determinant for the signaling profile of D receptor ligands. We therefore hypothesized that variations in receptor expression could influence D receptor response to antiparkinsonian drugs, most notably with respect to the recruitment bias between G and β-arrestin2.

Receptor density influences ligand-induced dopamine D receptor homodimerization.

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.