Dopamine in Health and Disease: Much More Than a Neurotransmitter

Abstract

Dopamine is derived from an amino acid, phenylalanine, which must be obtained through the diet. Dopamine, known primarily to be a neurotransmitter involved in almost any higher executive action, acts through five types of G-protein-coupled receptors. Dopamine has been studied extensively for its neuronal handling, synaptic actions, and in relation to Parkinson’s disease. However, dopamine receptors can be found extra-synaptically and, in addition, they are not only expressed in neurons, but in many types of mammalian cells, inside and outside the central nervous system (CNS). Recent studies show a dopamine link between the gut and the CNS; the mechanisms are unknown, but they probably require cells to act as mediators and the involvement of the immune system. In fact, dopamine receptors are expressed in almost any cell of the immune system where dopamine regulates various processes, such as antigen presentation, T-cell activation, and inflammation. This likely immune cell-mediated linkage opens up a new perspective for the use of dopamine-related drugs, i.e., agonist–antagonist–allosteric modulators of dopamine receptors, in a variety of diseases.

Ingestion of Lactobacillus rhamnosus modulates chronic stress-induced feather pecking in chickens

“…In parallel, pro-inflammatory cascades are also associated with increased phenylalanine hydroxylase (PAH) activity 21 , which metabolizes PHE to TYR and is reflected by the PHE/TYR ratio. In chronic episodes of immune activation, PHE and PHE/TYR ratio are elevated at the expense of dopamine 82 , a neurotransmitter which has actions on both the nervous and the immune systems 83 and is involved in gut-brain signaling 84 . Further down the PHE-TYR-Dopamine pathway, norepinephrine differentially regulates naive and effector CD8 + T cell activity 85 and decreases functionality and proliferation of CD8 + T cell 86 .…”

5-Hydroxytryptamine, Glutamate, and ATP: Much More Than Neurotransmitters

“…There is evidence of a link between the gut and the brain that is somehow mediated by 5-HT (Hooper et al, 2012;Carabotti et al, 2015). This has also been demonstrated for dopamine and it is a hot topic in relationship with Parkinson's disease (see Franco et al, 2021 for recent review). Among the most likely mechanisms of intercommunication, cells of the immune system may be mediators that respond to 5-HT due to the expression of some of its receptors.…”

Dopamine Transporter Genetic Reduction Induces Morpho-Functional Changes in the Enteric Nervous System

“…Specifically, antidopaminergic gastrointestinal prokinetics (e.g., domperidone, metoclopramide, levosulpiride) are commercially available to alleviate foregut motor disorders, including functional dyspepsia, gastroesophageal reflux disease and gastroparesis [ 34 ]. Moreover, changes in DAT availability have been associated to gastrointestinal dysfunctions in Parkinson’s patients [ 35 ] as well as in psychiatric disorders [ 13 ].…”

“…Indeed, the possibility to elucidate the role of DAT in the gut as well as its influence on neurotransmitter pathways within the ENS, may strengthen the causal relationship between development of brain disorders associated to gastrointestinal comorbidities, such as addictive disorders, attention-deficit/hyperactivity disorder, schizophrenia, Parkinson’s disease and dopaminergic system dysregulation. This is all the more interesting since psychostimulants, used as addictive drugs, or several antidopaminergic drugs, prescribed as prokinetics [ 11 ] or antipsychotics [ 12 ], show relevant gastrointestinal symptoms [ 13 ].…”