Production of functional recombinant G-protein coupled receptors for heteromerization studies

Čavić, Milena; Lluı́s, Carme; Moreno, Estefanía; Bakešová, Jana; Canela, Enric I.; Navarro, Gemma

doi:10.1016/j.jneumeth.2011.05.021

Cited by 8 publications

(3 citation statements)

References 11 publications

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“…On the basis of this interaction, some studies of heterotetrameric structures have been proposed for D1R-D3R and adenosine A2Areceptor (A2AR)-D2R heteromers (Cortés et al, 2016). It is widely known that A2AR antagonists have been proposed as potential drugs for the treatment of Parkinson's disease (Cavić et al, 2011). Interestingly, existing research has also decoded the signaling of a GPCR heteromeric complex, which may reveal therapeutic strategies for disorders including Parkinson, schizophrenia and dementia (Fribourg et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Dopamine and Dopamine Receptors in Alzheimer's Disease: A Systematic Review and Network Meta-Analysis

Pan

Kaminga

Wen

et al. 2019

Front. Aging Neurosci.

176

128

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Background: The dopaminergic system has been associated with the progression of Alzheimer's disease. But previous studies found inconsistent results regarding the relationship between Alzheimer's disease and dopamine when looking at dopamine receptor concentrations. Objective: The aim of this review was to synthesize, using a random-effects model of meta-analysis, the link between the dopaminergic system and Alzheimer's disease. Methods: A detailed analysis protocol was registered at the PROSPERO database prior to data extraction (CRD42018110798). Electronic databases of PubMed, Embase, Web of Science, and Psyc-ARTICLES were searched up to December 2018 for studies that examined dopamine and dopamine receptors in relation to Alzheimer's disease. Standardized mean differences (SMD) were calculated to assess group differences in the levels of dopaminergic neurometabolites. Results: Seventeen studies met the eligibility criteria. Collectively, they included 512 patients and 500 healthy controls. There were significantly lower levels of dopamine in patients with Alzheimer's disease compared with controls (SMD = −1.56, 95% CI: −2.64 to −0.49). In addition, dopamine 1 receptor (SMD = −5.05, 95% CI: −6.14 to −3.97) and dopamine 2 receptor (SMD = −1.13, 95% CI: −1.52 to −0.74) levels were decreased in patients with Alzheimer's disease compared with controls. The results of network meta-analysis indicated that the rank of correlation with Alzheimer's disease from highest to lowest was dopamine (0.74), dopamine 2 receptor (0.49), dopamine 3 receptor (0.46), dopamine 4 receptor (0.33), dopamine 5 receptor (0.31), and dopamine 1 receptor (0.64). Conclusions: Overall, decreased levels of dopaminergic neurotransmitters were linked with the pathophysiology of Alzheimer's disease. Nonetheless, there is a clear need for more prospective studies to validate these hypotheses.

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Section: Discussionmentioning

confidence: 99%

Dopamine and Dopamine Receptors in Alzheimer's Disease: A Systematic Review and Network Meta-Analysis

Pan

Kaminga

Wen

et al. 2019

Front. Aging Neurosci.

176

128

View full text Add to dashboard Cite

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“…At the end of the twentieth and beginning of the twenty-first century, several biophysical techniques, such as atomic force microscopy (AFM), bimolecular fluorescence complementation (BiFC), fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET), in situ proximity ligation assay (PLA), and AlphaScreen technology, were developed that allow the detection of spatial proximity of protein molecules, and such techniques have also been applied to A 2A and D 2 receptors [85,[91][92][93][94][95][96][97][98][99][100]. The results of these techniques and the observed co-aggregation, co-internalization and co-immuno-precipitation of A 2A R and D 2 R indicate that both receptors are at very close distance in biological membranes (<10 nm) and form heteromers.…”

Section: A 2a R and D 2 R Are At Very Close Distance In Biomembranes mentioning

confidence: 99%

Allosteric Interactions between Adenosine A2A and Dopamine D2 Receptors in Heteromeric Complexes: Biochemical and Pharmacological Characteristics, and Opportunities for PET Imaging

Prasad

Vries

Elsinga

et al. 2021

IJMS

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Adenosine and dopamine interact antagonistically in living mammals. These interactions are mediated via adenosine A2A and dopamine D2 receptors (R). Stimulation of A2AR inhibits and blockade of A2AR enhances D2R-mediated locomotor activation and goal-directed behavior in rodents. In striatal membrane preparations, adenosine decreases both the affinity and the signal transduction of D2R via its interaction with A2AR. Reciprocal A2AR/D2R interactions occur mainly in striatopallidal GABAergic medium spiny neurons (MSNs) of the indirect pathway that are involved in motor control, and in striatal astrocytes. In the nucleus accumbens, they also take place in MSNs involved in reward-related behavior. A2AR and D2R co-aggregate, co-internalize, and co-desensitize. They are at very close distance in biomembranes and form heteromers. Antagonistic interactions between adenosine and dopamine are (at least partially) caused by allosteric receptor–receptor interactions within A2AR/D2R heteromeric complexes. Such interactions may be exploited in novel strategies for the treatment of Parkinson’s disease, schizophrenia, substance abuse, and perhaps also attention deficit-hyperactivity disorder. Little is known about shifting A2AR/D2R heteromer/homodimer equilibria in the brain. Positron emission tomography with suitable ligands may provide in vivo information about receptor crosstalk in the living organism. Some experimental approaches, and strategies for the design of novel imaging agents (e.g., heterobivalent ligands) are proposed in this review.

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“…Changes in expression and activation of these CBRs, as well as their ability to form distinct functional heteromers with many other receptors alter the cell's tumuorigenic potential and their signalling properties, leading to pharmacologically different outcomes upon their stimulation [10][11][12]. Thus, the same ECS component can exert both protective and pathogenic effects in different tumour subtypes, which are often pathologically driven by different biological factors.…”

Section: The Interplay Between Cancer Biology and The Endocannabinoidmentioning

confidence: 99%

The Interplay between Cancer Biology and the Endocannabinoid System—Significance for Cancer Risk, Prognosis and Response to Treatment

Moreno

Čavić

Krivokuća

et al. 2020

Cancers

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The various components of the endocannabinoid system (ECS), such as the cannabinoid receptors (CBRs), cannabinoid ligands, and the signalling network behind it, are implicated in several tumour-related states, both as favourable and unfavourable factors. This review analyses the ECS’s complex involvement in the susceptibility to cancer, prognosis, and response to treatment, focusing on its relationship with cancer biology in selected solid cancers (breast, gastrointestinal, gynaecological, prostate cancer, thoracic, thyroid, CNS tumours, and melanoma). Changes in the expression and activation of CBRs, as well as their ability to form distinct functional heteromers affect the cell’s tumourigenic potential and their signalling properties, leading to pharmacologically different outcomes. Thus, the same ECS component can exert both protective and pathogenic effects in different tumour subtypes, which are often pathologically driven by different biological factors. The use of endogenous and exogenous cannabinoids as anti-cancer agents, and the range of effects they might induce (cell death, regulation of angiogenesis, and invasion or anticancer immunity), depend in great deal on the tumour type and the specific ECS component that they target. Although an attractive target, the use of ECS components in anti-cancer treatment is still interlinked with many legal and ethical issues that need to be considered.

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Production of functional recombinant G-protein coupled receptors for heteromerization studies

Cited by 8 publications

References 11 publications

Dopamine and Dopamine Receptors in Alzheimer's Disease: A Systematic Review and Network Meta-Analysis

Dopamine and Dopamine Receptors in Alzheimer's Disease: A Systematic Review and Network Meta-Analysis

Allosteric Interactions between Adenosine A2A and Dopamine D2 Receptors in Heteromeric Complexes: Biochemical and Pharmacological Characteristics, and Opportunities for PET Imaging

The Interplay between Cancer Biology and the Endocannabinoid System—Significance for Cancer Risk, Prognosis and Response to Treatment

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