Dopamine in Health and Disease: Much More Than a Neurotransmitter.

Rafael Franco,Gemma Navarro,Irene Reyes-Resina

doi:10.3390/biomedicines9020109

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.

Highlights

Studies with animal models of Parkinson’s disease (PD) have suggested that the motor disturbances are due to a disbalance in the so-called direct and indirect striatal pathways, in which neurons projecting to the globus pallidus and substantia nigra pars reticulata have two different types of dopamine receptors (D1 or D2 ; five DA receptor types have been discovered; see below)
This review presents information about dopamine that has mainly been obtained from enzymatic studies, and about the link with PD, without forgetting the actions that DA exerts in the periphery
Splice variants are mainly described for the D2 and the D4 receptors; importantly, other gene polymorphisms described for all five receptors, including single nucleotide polymorphism, may be associated with a variety of addictions and obesity [18,19,20,21,22,23,24,25]; other non-dopamine-receptor-related factors influence addictive behaviors

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Some to discover that the cause of PD was in the brain structures related to the striatum, and others showed that it was a lack of dopamine in the substantia nigra which, in turn, led to the depletion of DA in the striatum Soon after these early discoveries, L-DOPA was proposed as a medication to combat the symptoms of PD Studies with animal models of PD have suggested that the motor disturbances are due to a disbalance in the so-called direct and indirect striatal pathways, in which neurons projecting to the globus pallidus and substantia nigra pars reticulata have two different types of dopamine receptors (D1 or D2 ; five DA receptor types have been discovered; see below). Splice variants are mainly described for the D2 and the D4 receptors; importantly, other gene polymorphisms described for all five receptors, including single nucleotide polymorphism, may be associated with a variety of addictions (drugs, alcohol, etc.) and obesity [18,19,20,21,22,23,24,25]; other non-dopamine-receptor-related factors influence addictive behaviors

Features of DA Receptors That Are Important in Dopaminergic Transmission in

Dopamine Derivatives in Neurological and Neuropsychiatric Diseases

Dopamine in the Gastrointestinal Tract

Future Perspectives of DA as Neurotransmitter

Findings

Future Perspectives of DA as Regulatory Molecule