Cited by 2,763Receptor Mechanisms and SignalingNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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The Physiology, Signaling, and Pharmacology of Dopamine Receptors

Beaulieu, Jean-Martin, Gainetdinov, Raul R.·2011·Pharmacological Reviews

DOI 10.1124/pr.110.002642

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Abstract

G protein-coupled dopamine receptors (D1, D2, D3, D4, and D5) mediate all of the physiological functions of the catecholaminergic neurotransmitter dopamine, ranging from voluntary movement and reward to hormonal regulation and hypertension. Pharmacological agents targeting dopaminergic neurotransmission have been clinically used in the management of several neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, bipolar disorder, Huntington's disease, attention deficit hyperactivity disorder (ADHD(1)), and Tourette's syndrome. Numerous advances have occurred in understanding the general structural, biochemical, and functional properties of dopamine receptors that have led to the development of multiple pharmacologically active compounds that directly target dopamine receptors, such as antiparkinson drugs and antipsychotics. Recent progress in understanding the complex biology of dopamine receptor-related signal transduction mechanisms has revealed that, in addition to their primary action on cAMP-mediated signaling, dopamine receptors can act through diverse signaling mechanisms that involve alternative G protein coupling or through G protein-independent mechanisms via interactions with ion channels or proteins that are characteristically implicated in receptor desensitization, such as β-arrestins. One of the future directions in managing dopamine-related pathologic conditions may involve a transition from the approaches that directly affect receptor function to a precise targeting of postreceptor intracellular signaling modalities either directly or through ligand-biased signaling pharmacology. In this comprehensive review, we discuss dopamine receptor classification, their basic structural and genetic organization, their distribution and functions in the brain and the periphery, and their regulation and signal transduction mechanisms. In addition, we discuss the abnormalities of dopamine receptor expression, function, and signaling that are documented in human disorders and the current pharmacology and emerging trends in the development of novel therapeutic agents that act at dopamine receptors and/or on related signaling events.

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Authors: Beaulieu, J.-M., & Gainetdinov, R. R.
Affiliations: Université Laval (CA)
Italian Institute of Technology (IT)
ORCID: Beaulieu, Jean-Martin
Gainetdinov, Raul R.
Venue: Pharmacological Reviews
Publisher: Elsevier BV
Published: 2011-03
Volume: 63
Issue: 1
Pages: 182-217
ISSN: 0031-6997 (ISSN-L)
DOI: 10.1124/pr.110.002642
OpenAlex: W2097744565
Cited by: 2,763
References: 409
Citations by year: 2026: 157 · 2025: 183 · 2024: 172 · 2023: 193 · 2022: 201 · 2021: 197 · 2020: 198 · 2019: 220 · 2018: 200 · 2017: 187 · 2016: 205 · 2015: 175 · 2014: 194 · 2013: 136 · 2012: 101
FWCI: 13.93
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Pharmacological Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research (NSA93798)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: dopamine receptors, dopamine D1/D5 receptors, G protein-coupled receptors, signal transduction, cAMP signaling, G protein-independent signaling, beta-arrestin, receptor desensitization, antiparkinsonian drugs, antipsychotic drugs
MeSH terms: Animals, Gene Expression Regulation, Humans, Ligands, Receptors, Dopamine, Signal Transduction, Dopamine Agonists, Dopamine Antagonists, Molecular Targeted Therapy

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