Dopamine Receptor Signaling

@article{Neve2004DopamineRS,
  title={Dopamine Receptor Signaling},
  author={Kim A. Neve and Jeremy K. Seamans and Heather Trantham-Davidson},
  journal={Journal of Receptors and Signal Transduction},
  year={2004},
  volume={24},
  pages={165 - 205}
}
The D1-like (D1, D5) and D2-like (D2, D3, D4) classes of dopamine receptors each has shared signaling properties that contribute to the definition of the receptor class, although some differences among subtypes within a class have been identified. D1-like receptor signaling is mediated chiefly by the heterotrimeric G proteins Gαs and Gαolf, which cause sequential activation of adenylate cyclase, cylic AMP-dependent protein kinase, and the protein phosphatase-1 inhibitor DARPP-32. The increased… 

Regulation of dopamine D3 receptors by protein-protein interactions

TLDR
Findings reveal a prototypic protein association model between a G protein-coupled receptor and CaMKII, which can inhibit the receptor function and further regulate the behavioral response to the psychostimulant cocaine.

Regulation of dopamine D3 receptors by protein-protein interactions

TLDR
A prototypic protein association model between a G protein-coupled receptor and CaMKII is revealed, which reveals the abundance, turnover cycle, and function of D3R can be regulated by multiple signals and enzymatic proteins.

Evidence That Calmodulin Binding to the Dopamine D2 Receptor Enhances Receptor Signaling

TLDR
Findings suggest that binding of CaM to the dopamine D2 receptor enhances D1 receptor signaling, and mutation of three of these residues in the full-length receptor decreased the coprecipitation of the D2 receptors and CaM and also significantly decreased D2ceptor signaling, without altering the coupling of the receptor to G proteins.

Dopamine D1 Receptor Signaling: Does GαQ–Phospholipase C Actually Play a Role?

TLDR
This Minireview examines 30 years of relevant literature and proposes that the data strongly favor alternate hypotheses: first, that SKF-83959 is a typical D1 partial agonist; and second, that the reported activation of PLC bySKF- 83959 and related benzazepines likely is due to off-target effects, not actions at D1 receptors.

Regulation of the Dopamine D1-D2 Receptor Heterooligomer

TLDR
The results indicated that desensitization of the D1-D2 receptor heteromer mediated calcium signal can occur by agonist occupancy even without activation and is regulated by two distinct functions of GRK2.

A Dopamine D2 Receptor Mutant Capable of G Protein-Mediated Signaling but Deficient in Arrestin Binding

TLDR
Results imply that the sequence IYIV212-215 at the N terminus of IC3 of the D2 receptor is a key element of the arrestin binding site, consistent with previous suggestions that the differential effects of D2 and D3 receptor activation on membrane translocation of arrestin and receptor internalization are due, at least in part, to differential phosphorylation of the receptors.

D1–D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum

TLDR
Evidence that the D1–D2 signaling complex can be more readily detected in mice that are 8 months in age compared with animals that are 3 months old is provided, suggesting that calcium signaling through the D2 dopamine receptor complex is relevant for function in the postadolescent brain.

D5 Dopamine Receptors are Required for Dopaminergic Activation of Phospholipase C

TLDR
D5 receptors are required for dopamine and selective D1-like agonists to induce phospholipase C-mediated phosphoinositide signaling in the mammalian brain.

Dopamine Receptor Signaling: Intracellular Pathways to Behavior

TLDR
This chapter discusses canonical and non-canonical signaling pathways regulated by individual dopamine receptor subtypes and the contribution of these pathways to dopamine-induced behaviors in the behavioral effects of drugs of abuse, including cocaine, amphetamine, and methamphetamine.

Dopamine-induced functional activation of Gαq mediated by dopamine D1-like receptor in rat cerebral cortical membranes

TLDR
Dopamine-stimulated Gαq functionality was highest in cortex as compared to hippocampus or striatum, and the responses induced by SKF83566, R(+)-SCH23390, and pergolide were most likely mediated by 5-HT2A receptor, but not by dopamine D1-like receptor.
...

References

SHOWING 1-10 OF 282 REFERENCES

G protein-mediated mitogen-activated protein kinase activation by two dopamine D2 receptors.

TLDR
Results suggest that D2L- and D2S-mediated MAPK activation is predominantly Gbetagamma subunit-mediated signaling and that protein kinase C and tyrosine phosphorylations are involved in these signaling pathways.

Activation of type II adenylate cyclase by D2 and D4 but not D3 dopamine receptors.

TLDR
It is proposed that activation of both D2L and D4.4 dopamine receptors potentiated phorbol-12-myristate-13-acetate-stimulated ACII activity through the release of betagamma subunits from pertussis toxin-sensitive G proteins.

The D2s dopamine receptor stimulates phospholipase D activity: a novel signaling pathway for dopamine.

TLDR
A novel signaling pathway for the D2s is described, which is the activation of phospholipase D (PLD), which was found to correlate with the presence of a specific protein kinase C isoform, PKCepsilon, indicating that the stimulation of PLD may involve Rho family members.

Adenylyl Cyclase Interaction with the D2 Dopamine Receptor Family; Differential Coupling to Gi, Gz, and Gs

TLDR
It is demonstrated for the first time that the two D3 receptor isoforms, and not any of the other D2 receptor subtypes, also couple to Gs in both COS-7 and CHO transfected cells, in the presence of PTX.

Coupling of D 1 and Dopamine Receptors to Multiple G Proteins Implications for Understanding the Diversity in Receptor-G Protein Coupling

Dopamine receptors are a subclass of the super family of G protein-coupled receptors, that transduce their effects by coupling to specific G proteins. Within the dopamine receptor family, the

Binding of Calmodulin to the D2-Dopamine Receptor Reduces Receptor Signaling by Arresting the G Protein Activation Switch*

TLDR
The biochemical basis for a cross-talk between intracellular Ca2+ and the D2 receptor is described and inhibition by CaM does not result from uncoupling the D 2 receptor from its cognate G protein(s); rather, CaM directly targets the D1 receptor to block the receptor-operated G protein activation switch.

SH3 binding domains in the dopamine D4 receptor.

TLDR
The data indicates that the D4 receptor contains SH3 binding sites and that these sites fall within a region involved in the control of receptor internalization, which may account for the deficiency in functional activation of second messengers.

Selective reconstitution of human D4 dopamine receptor variants with Gi alpha subtypes.

TLDR
It is confirmed that loop i3 is required for D4 receptors to activate G proteins, and the polymorphic region of the loop does not appear to affect the specificity or efficiency of G(i)alpha coupling.

Dopamine activation of the arachidonic acid cascade as a basis for D1D2 receptor synergism

TLDR
In Chinese hamster ovary cells transfected with the D2 receptor complementary DNA, D2 agonists potently enhance arachidonic acid release, provided that such release has been initiated by stimulating constitutive purinergic receptors or by increasing intracellular Ca2+.

Activation of Go-coupled Dopamine D2 Receptors Inhibits ERK1/ERK2 in Pituitary Cells

TLDR
The data suggest that ERK 1/2 suppression is an obligatory step in the dopaminergic control of prolactin gene transcription and that bidirectional control of ERK1/2 function in the pituitary may provide a key mechanism for endocrine gene control.
...