Adenosine A2A Receptors: Localization and Function

Simola, Nicola; Wardas, Jadwiga

doi:10.1007/978-3-319-20273-0_1

Cited by 3 publications

(4 citation statements)

References 191 publications

(201 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inactivation of extracellular adenosine following the uptake of the nucleoside back into the cell by the aforementioned transporters occurs by: (1) the phosphorylation of AMP by adenosine kinase (AKA); (2) the deamination of adenosine to inosine in a reaction catalyzed by adenosine deaminase (ADA); and (3) a reversible reaction catalyzed by SAH hydrolase leading to the synthesis of SAH from adenosine and L-homocysteine [ 184 , 185 , 190 ].…”

Section: Adenosine and Its Receptors—the Role In Etmentioning

confidence: 99%

“…Additionally, an activated A2B receptor stimulates phospholipase C (PLC) activity. Regarding A1 receptors, apart from their effect on AC, their action may also involve other signal transduction mechanisms, e.g., the inhibition of voltage-dependent Ca 2+ channels and the stimulation of K + channels [ 182 , 184 , 191 ].…”

Section: Adenosine and Its Receptors—the Role In Etmentioning

confidence: 99%

“…Description in the text. A1, A2A, A2B, and A3: adenosine receptors, AC: adenylate cyclase, ADA: adenosine deaminase, ADP: adenosine 5′-diphosphate, AKA: adenosine kinase, ATP: adenosine 5′-triphosphate, cAMP: cyclic adenosine-3′,5′-monophosphate, ecto-5′-NT: ecto-5′-nucleotidase, ENT: nucleoside transporter, 5′-AMP: adenosine 5′-monophosphate, 5′-NT: 5′-nucleotidase, SAH: S-adenosylhomocysteine, PKA: protein kinase A, PKC: protein kinase C, PLC: phospholipase C (based on research [ 183 , 184 , 185 ]).…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

Kosmowska

Wardas

2021

Biomolecules

Self Cite

View full text Add to dashboard Cite

Essential tremor (ET) is one of the most common neurological disorders that often affects people in the prime of their lives, leading to a significant reduction in their quality of life, gradually making them unable to independently perform the simplest activities. Here we show that current ET pharmacotherapy often does not sufficiently alleviate disease symptoms and is completely ineffective in more than 30% of patients. At present, deep brain stimulation of the motor thalamus is the most effective ET treatment. However, like any brain surgery, it can cause many undesirable side effects; thus, it is only performed in patients with an advanced disease who are not responsive to drugs. Therefore, it seems extremely important to look for new strategies for treating ET. The purpose of this review is to summarize the current knowledge on the pathomechanism of ET based on studies in animal models of the disease, as well as to present and discuss the results of research available to date on various substances affecting dopamine (mainly D3) or adenosine A1 receptors, which, due to their ability to modulate harmaline-induced tremor, may provide the basis for the development of new potential therapies for ET in the future.

show abstract

Section: Adenosine and Its Receptors—the Role In Etmentioning

confidence: 99%

Section: Adenosine and Its Receptors—the Role In Etmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

Kosmowska

Wardas

2021

Biomolecules

Self Cite

View full text Add to dashboard Cite

show abstract

“…These receptors belong to G‐protein coupled receptor family, with the following four sub‐types: A 1 , A 2A , A 2B , and A 3 . Among these, A 2A receptors appear to play the most important role in controlling motor activities and modulation of dopamine‐mediated responses (Simola & Wardas, 2015). Adenosine A 2A receptors (AA 2A R) are highly distributed in the central nervous system and are found in abundance in the basal ganglia, a region of the brain associated with motor function (Kitta et al, 2016; Pinna, 2014; Yamada et al, 2014; Zheng et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of five‐membered heterocyclic derivatives of istradefylline with comparable pharmacological activity

Wang

Wang²,

Xu³

et al. 2022

Chem Biol Drug Des

View full text Add to dashboard Cite

Parkinson's disease (PD) is a common degenerative disease of the central nervous system among the elderly. Istradefylline, an FDA-approved adenosine A 2A receptor antagonist (anti-PD drug), has good efficacy. However, it has been reported that the double bond of istradefylline is easily converted into cis-configuration when exposed to an indoor environment or direct light in a dilute solution. In order to find more stable adenosine A 2A receptor antagonists with similar pharmacological efficacy to istradefylline, the compounds series I-1 (12 compounds) was designed by maintaining the xanthine skeleton of istradefylline unchanged and replacing the trans-double bond with thiazole or benzothiazole and other biologically active heterocyclic compounds. These compounds were synthesized via multi-step experiment and successfully confirmed through different characterization techniques for their ability to inhibit cAMP formation in A 2A AR overexpressing cells. The thiazole derivative of istradefylline (Compound I-1-11, I-1-12) exhibited significant activity (IC 50 = 16.74 ± 4.11 μM, 10.36 ± 3.09 μM), as compared to istradefylline (IC 50 = 5.05 ± 1.32 μM). In addition, the molecular docking of benzothiazole derivatives I-1-11 and thiazole derivatives I-1-12 with higher inhibition rate were carried out and compared with istradefylline. The molecular docking results showed that I-1-11 and I-1-12 anchored in the same site as that of XAC (3REY) with predicted affinity binding energy −6.63 kcal/ mol and − 6.75 kcal/mol, respectively. Validation through dynamics simulation also showed stable interactions, with fluctuations <3 Å and MM/GBSA energy <−20 kcal/mol. Hence, this study could provide a basis for the rational design of adenosine A 2A receptor antagonists with better potency.

show abstract

Potential antipsychotic action of the selective agonist of adenosine A1 receptors, 5′-Cl-5′-deoxy-ENBA, in amphetamine and MK-801 rat models

2020

Self Cite

View full text Add to dashboard Cite

Background Disturbances of dopaminergic and glutamatergic transmissions have been suggested to be involved in the pathomechanisms underlying psychotic symptoms of schizophrenia. In line with this concept, hyperlocomotion induced by the dopaminomimetic amphetamine and the uncompetitive antagonist of NMDA receptors MK-801 (dizocilpine) in rodents is a generally established model for screening of new potential antipsychotic drugs. Since recent studies have indicated that receptors for adenosine may be targets for antipsychotic therapy, the aim of the present study was to investigate an influence of 5′-Cl-5′-deoxy-ENBA, a potent and selective adenosine A 1 receptor agonist, on hyperlocomotion induced by amphetamine and MK-801. Methods Locomotor activity was measured by Force Plate Actimeters where four force transducers located below the corners of the floor of the cage tracked the animal position on a Cartesian plane at each time point. Results Hyperlocomotion induced by either amphetamine (1 mg/kg sc) or MK-801 (0.3 mg/kg ip) was inhibited by 5′-Cl-5′deoxy-ENBA (0.1 mg/kg ip). The effect of 5′-Cl-5′-deoxy-ENBA on the amphetamine-and MK-801-induced hyperlocomotion was antagonized by the selective antagonist of adenosine A 1 receptor DPCPX at doses of 1 and 2 mg/kg ip, respectively. Conclusion The present study suggests that stimulation of adenosine A 1 receptors may produce antipsychotic effects.

show abstract

Adenosine A2A Receptors: Localization and Function

Cited by 3 publications

References 191 publications

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

Design and synthesis of five‐membered heterocyclic derivatives of istradefylline with comparable pharmacological activity

Potential antipsychotic action of the selective agonist of adenosine A1 receptors, 5′-Cl-5′-deoxy-ENBA, in amphetamine and MK-801 rat models

Contact Info

Product

Resources

About