Immunomodulatory Effects Mediated by Dopamine

Abstract

Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers.

Figure 1

Metabolic pathways associated with DA. The metabolic pathways branching from the catabolism of L-phenylalanine are shown. (a) The dark blue arrows (over light yellow branches) indicate the DA generation pathway, and the red arrows (over light green branches) represent the noradrenaline and adrenaline pathway. Green arrows (over orange branches) show the alternative synthesis pathways to dopamine. The magenta arrows (over pink branches) show dopamine catabolism; the right side shows the normal pathways converging on HVA; the left side shows the catabolic pathways when dopamine concentrations are high in the cytoplasm. Many enzymes can transform dopamine and metabolites, such as COX enzymes (cyclooxygenases), producing dopaminochrome and dopamine quinone [44]. Other enzymes can produce sulfur and glucuronide derivatives. (b) The inset shows the most important products (circled with dotted lines) of metabolic pathways associated with DA. The compounds in these pathways are denoted by Kyoto Encyclopedia of Genes and Genomes (KEGG) code (http://www.genome.jp/kegg/). Enzymes with their classification codes (EC, http://www.chem.qmul.ac.uk/iubmb/enzyme/) and UNIPROT gene names are shown in squares.