Current Concepts on the Physiopathological Relevance of Dopaminergic Receptors

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2017 Feb 24

PMID 28228718

Citations 30

Authors

Ada Ledonne

Nicola B Mercuri

Affiliations

Soon will be listed here.

Abstract

Dopamine (DA) is a key neurotransmitter modulating essential functions of the central nervous system (CNS), like voluntary movement, reward, several cognitive functions and goal-oriented behaviors. The factual relevance of DAergic transmission can be well appreciated by considering that its dysfunction is recognized as a core alteration in several devastating neurological and psychiatric disorders, including Parkinson's disease (PD) and associated movement disorders, as well as, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD) and addiction. Here we present an overview of the current knowledge on the involvement of DAergic receptors in the regulation of key physiological brain activities, and the consequences of their dysfunctions in brain disorders such as PD, schizophrenia and addiction.

Citing Articles

Drug inhibition and substrate transport mechanisms of human VMAT2.

Wei F, Liu H, Zhang W, Wang J, Zhang Y Nat Commun. 2025; 16(1):323.

PMID: 39747030 PMC: 11695631. DOI: 10.1038/s41467-024-55361-0.

The dopaminergic system and Alzheimer's disease.

Zhang Y, Liang Y, Gu Y Neural Regen Res. 2024; 20(9):2495-2512.

PMID: 39314145 PMC: 11801300. DOI: 10.4103/NRR.NRR-D-24-00230.

Linkers in Bitopic Agonists Shape Bias Profile among Transducers for the Dopamine D2 and D3 Receptors.

Semeano A, Garland R, Bonifazi A, Lee K, Famiglietti J, Zhang W ACS Pharmacol Transl Sci. 2024; 7(8):2333-2349.

PMID: 39144557 PMC: 11320723. DOI: 10.1021/acsptsci.4c00119.

Tyrosine Hydroxylase Inhibitors and Dopamine Receptor Agonists Combination Therapy for Parkinson's Disease.

Yi L, Tan E, Zhou Z Int J Mol Sci. 2024; 25(9).

PMID: 38731862 PMC: 11083272. DOI: 10.3390/ijms25094643.

Design and Synthesis of DR Bitopic Ligands with Flexible Secondary Binding Fragments: Radioligand Binding and Computational Chemistry Studies.

Tian G, Hsieh C, Taylor M, Lee J, Luedtke R, Mach R Molecules. 2024; 29(1).

PMID: 38202706 PMC: 10779535. DOI: 10.3390/molecules29010123.

References

Reavill C, Taylor S, Wood M, Ashmeade T, Austin N, Avenell K . Pharmacological actions of a novel, high-affinity, and selective human dopamine D(3) receptor antagonist, SB-277011-A. J Pharmacol Exp Ther. 2000; 294(3):1154-65. View

Lee S, So C, Rashid A, Varghese G, Cheng R, Lanca A . Dopamine D1 and D2 receptor Co-activation generates a novel phospholipase C-mediated calcium signal. J Biol Chem. 2004; 279(34):35671-8. DOI: 10.1074/jbc.M401923200. View

Schultz W, Dayan P, Montague P . A neural substrate of prediction and reward. Science. 1997; 275(5306):1593-9. DOI: 10.1126/science.275.5306.1593. View

Calabresi P, Maj R, Mercuri N, Bernardi G . Coactivation of D1 and D2 dopamine receptors is required for long-term synaptic depression in the striatum. Neurosci Lett. 1992; 142(1):95-9. DOI: 10.1016/0304-3940(92)90628-k. View

Sun H, Calipari E, Beveridge T, Jones S, Chen R . The brain gene expression profile of dopamine D2/D3 receptors and associated signaling proteins following amphetamine self-administration. Neuroscience. 2015; 307:253-61. PMC: 4591251. DOI: 10.1016/j.neuroscience.2015.08.053. View

Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O . Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature. 1997; 385(6617):634-6. DOI: 10.1038/385634a0. View

Le Foll B, Gallo A, Le Strat Y, Lu L, Gorwood P . Genetics of dopamine receptors and drug addiction: a comprehensive review. Behav Pharmacol. 2009; 20(1):1-17. DOI: 10.1097/FBP.0b013e3283242f05. View

Mango D, Bonito-Oliva A, Ledonne A, Nistico R, Castelli V, Giorgi M . Phosphodiesterase 10A controls D1-mediated facilitation of GABA release from striato-nigral projections under normal and dopamine-depleted conditions. Neuropharmacology. 2013; 76 Pt A:127-36. DOI: 10.1016/j.neuropharm.2013.08.010. View

Rocchetti J, Isingrini E, Bo G, Sagheby S, Menegaux A, Tronche F . Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus. Biol Psychiatry. 2014; 77(6):513-25. DOI: 10.1016/j.biopsych.2014.03.013. View

10.

Gold S, Hoang C, Potts B, Porras G, Pioli E, Kim K . RGS9-2 negatively modulates L-3,4-dihydroxyphenylalanine-induced dyskinesia in experimental Parkinson's disease. J Neurosci. 2007; 27(52):14338-48. PMC: 6673430. DOI: 10.1523/JNEUROSCI.4223-07.2007. View

11.

Villar V, Jones J, Armando I, Palmes-Saloma C, Yu P, Pascua A . G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor. J Biol Chem. 2009; 284(32):21425-34. PMC: 2755867. DOI: 10.1074/jbc.M109.003665. View

12.

Kravitz A, Freeze B, Parker P, Kay K, Thwin M, Deisseroth K . Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature. 2010; 466(7306):622-6. PMC: 3552484. DOI: 10.1038/nature09159. View

13.

Gross G, Drescher K . The role of dopamine D(3) receptors in antipsychotic activity and cognitive functions. Handb Exp Pharmacol. 2012; (213):167-210. DOI: 10.1007/978-3-642-25758-2_7. View

14.

Hikida T, Kimura K, Wada N, Funabiki K, Nakanishi S . Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior. Neuron. 2010; 66(6):896-907. DOI: 10.1016/j.neuron.2010.05.011. View

15.

Perreault M, Hasbi A, ODowd B, George S . Heteromeric dopamine receptor signaling complexes: emerging neurobiology and disease relevance. Neuropsychopharmacology. 2013; 39(1):156-68. PMC: 3857642. DOI: 10.1038/npp.2013.148. View

16.

Perreault M, Fan T, Alijaniaram M, ODowd B, George S . Dopamine D1-D2 receptor heteromer in dual phenotype GABA/glutamate-coexpressing striatal medium spiny neurons: regulation of BDNF, GAD67 and VGLUT1/2. PLoS One. 2012; 7(3):e33348. PMC: 3299775. DOI: 10.1371/journal.pone.0033348. View

17.

Yang J, Ye M, Tian C, Yang M, Wang Y, Shu Y . Dopaminergic modulation of axonal potassium channels and action potential waveform in pyramidal neurons of prefrontal cortex. J Physiol. 2013; 591(13):3233-51. PMC: 3717225. DOI: 10.1113/jphysiol.2013.251058. View

18.

Traynor J, Terzi D, Caldarone B, Zachariou V . RGS9-2: probing an intracellular modulator of behavior as a drug target. Trends Pharmacol Sci. 2009; 30(3):105-11. PMC: 3394094. DOI: 10.1016/j.tips.2008.11.006. View

19.

Giros B, Sokoloff P, Martres M, Riou J, Emorine L, Schwartz J . Alternative splicing directs the expression of two D2 dopamine receptor isoforms. Nature. 1989; 342(6252):923-6. DOI: 10.1038/342923a0. View

20.

Watanabe H, Xu J, Bengra C, Jose P, Felder R . Desensitization of human renal D1 dopamine receptors by G protein-coupled receptor kinase 4. Kidney Int. 2002; 62(3):790-8. DOI: 10.1046/j.1523-1755.2002.00525.x. View