Where Is Dopamine and how do Immune Cells See it?: Dopamine-Mediated Immune Cell Function in Health and Disease

Abstract

Dopamine is well recognized as a neurotransmitter in the brain, and regulates critical functions in a variety of peripheral systems. Growing research has also shown that dopamine acts as an important regulator of immune function. Many immune cells express dopamine receptors and other dopamine related proteins, enabling them to actively respond to dopamine and suggesting that dopaminergic immunoregulation is an important part of proper immune function. A detailed understanding of the physiological concentrations of dopamine in specific regions of the human body, particularly in peripheral systems, is critical to the development of hypotheses and experiments examining the effects of physiologically relevant dopamine concentrations on immune cells. Unfortunately, the dopamine concentrations to which these immune cells would be exposed in different anatomical regions are not clear. To address this issue, this comprehensive review details the current information regarding concentrations of dopamine found in both the central nervous system and in many regions of the periphery. In addition, we discuss the immune cells present in each region, and how these could interact with dopamine in each compartment described. Finally, the review briefly addresses how changes in these dopamine concentrations could influence immune cell dysfunction in several disease states including Parkinson's disease, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, as well as the collection of pathologies, cognitive and motor symptoms associated with HIV infection in the central nervous system, known as NeuroHIV. These data will improve our understanding of the interactions between the dopaminergic and immune systems during both homeostatic function and in disease, clarify the effects of existing dopaminergic drugs and promote the creation of new therapeutic strategies based on manipulating immune function through dopaminergic signaling. Graphical Abstract.

Keywords: Catecholamine; Dopamine; Drug abuse; Immunopharmacology; Neuroimmunology; Neuropathogenesis.

Figure 1 -. Concentrations of Dopamine Throughout the Central Nervous System.

Range of dopamine concentrations found throughout the central nervous system, based on the summary of literature in Table 1. These values represent the range of calculated absolute molar values, which provide a simplified way to compare relative physiologically relevant concentrations across the brain. The dopaminergic pathways of the brain in which dopamine concentrations are the highest are highlighted; the nigrostriatal pathway starts in the substantia nigra and innervates the dorsal striatum (purple), the mesocortical pathway connects the ventral tegmental area to the cortex (blue), the mesolimbic pathway connects the ventral tegmental area to the limbic regions of the brain such as the amygdala and hippocampus (red), and the tuberoinfundibular pathway which runs from the hypothalamus to the pituitary (green). Concentrations in these regions change significantly during the use of illicit drugs (Table 2) and in different disease states (Table 4). For clarity, data showing concentrations that were outliers in the calculated range of concentrations for each region are excluded.

Figure 2 -. Concentrations of Dopamine Throughout the Periphery.

A graphical representation of the various concentrations of dopamine throughout the periphery, based on the summary literature contained in findings in Table 3. These values represent the range of calculated absolute molar values, which provide a simplified way to compare relative physiologically relevant concentrations across peripheral systems. These concentrations can change during different disease states (Table 4). For clarity, data showing concentrations that were outliers in the calculated range of concentrations for each region are excluded