Expression of Dopamine Receptors in Immune Regulatory Cells

Abstract

<b><i>Objective:</i></b> Parkinson’s disease (PD) patients are usually treated with L-dopa and/or dopaminergic agonists, which act by binding five types of dopaminergic receptors (DRD1–DRD5). Peripheral immune cells are known to express dopamine receptors on their membrane surface, and therefore they could be directly affected by the treatment. Regulatory cells are the main modulators of inflammation, but it is not clear whether dopaminergic treatment could affect their functions. While only regulatory T cells (Tregs) have been proved to express dopamine receptors, it is not known whether other regulatory cells such as CD8regs, regulatory B cells (Bregs), tolerogenic dendritic cells, and intermediate monocytes also express them. <b><i>Methods:</i></b> The expression of dopamine receptors in Tregs, CD8regs, Bregs, tolerogenic dendritic cells, and intermediate monocytes was herein evaluated. cDNA from 11 PD patients and 9 control subjects was obtained and analyzed. <b><i>Results:</i></b> All regulatory cell populations expressed the genes coding for dopamine receptors, and this expression was further corroborated by flow cytometry. These findings may allow us to propose regulatory populations as possible targets for PD treatment. <b><i>Conclusions:</i></b> This study opens new paths to deepen our understanding on the effect of PD treatment on the cells of the regulatory immune response.

Localisation of clozapine during experimental autoimmune encephalomyelitis and its impact on dopamine and its receptors

“…Interestingly, the regions with the highest clozapine levels are known to express a high density of DR1 and DR2, and the cerebellum, with low dopamine levels, has lower DR expression 54 . All DRs are reported to be widely expressed in the CNS and several studies have reported their expression on immune cells 11 , which play an important role in MS 50 . Moreover, DR expression on immune cells is also associated with some neurological and immune-related disorders 55,56 .…”

“…Clozapine antagonises dopamine receptors (DR), which can be separated into two subtypes, D1 subtypes (DR1 and DR5) and D2 subtypes (DR2, DR3 and DR4), based on modulation of cAMP production 10 . All DRs are highly expressed in the brain 10 and on immune cells 11 , and have shown to be involved in mental disorders and neuroinflammatory diseases like schizophrenia, depression, Parkinson's and Huntington's disease 12,13 . Given clozapine's affinity for DRs, it has been reported to displace dopamine from the receptor within less than one minute 14,15 , directing it towards other receptors and causing it to have unanticipated effects.…”

The Cross-Talk Between the Dopaminergic and the Immune System Involved in Schizophrenia

“…A number of catecholamine family members, including dopamine, have been extensively involved in the regulation of the immune response (Tracey, 2009), affecting both the innate and adaptive immune system (Pacheco et al, 2014;Vidal and Pacheco, 2019). In this regard, dopamine receptors are expressed on T and B lymphocytes, dendritic and NK cells, macrophages, microglia, intermediate monocytes, neutrophils, and eosinophils (Levite, 2016;Arce-Sillas et al, 2019). In this section we focused in the analysis of the dopaminergic regulation of T cells, microglia, and monocytes, since these immune cells have been implicated in cognitive functions.…”

Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma

“…Accordingly, treatment of primary microglial cultures with a DRD2/DRD3 agonist, increases the release of nitrite and IFN-γ [ 162 ]. Dopamine receptors are also expressed on dendritic cell, on natural killer (NK) cells, macrophages, microglia, intermediate monocytes, neutrophils, and eosinophils [ 163 ]. All these immune cells participate to both cognitive functions and the modulation of glioma microenvironment thus, these data highlight additional putative immunomodulatory roles of dopamine signaling [ 164 , 165 , 166 ].…”