Disease relevance of Adora2a

• In addition, A2AR supports myocardial contractility in a setting of low-flow ischemia [1].
• Receptor heteromerization in adenosine A2A receptor signaling: relevance for striatal function and Parkinson's disease [2].
• Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor [3].
• In addition, we show in a model of LPS-induced endotoxemia that inosine protected both A2aR-/- and A3R-/- mice from inflammation, but not A2aA3R double-null mice, indicating that in this model both A2aR and A3R were used by inosine [4].
• RESULTS: Adenosine A1, A2A, and A3 receptor agonists potentiated, whereas adenosine A2A receptor antagonists, but not A1 antagonists, reversed 3alpha, 5alpha THP-induced catalepsy [5].

Psychiatry related information on Adora2a

• Here we report that caffeine at 5, 10 and 15 mg kg(-1) increased wakefulness in both wild-type mice and A1 receptor knockout mice, but not in A2A receptor knockout mice [6].
• Since the clinical and neuropathological features of 3-NP-induced striatal damage resemble those observed in Huntington's disease, the results suggest that A2AR antagonism may be a potential therapeutic strategy in Huntington's disease patients [7].
• Arterial pressure and heart rate increase during REM sleep in adenosine A2A-receptor knockout mice, but not in wild-type mice [8].
• The presence of the A2aR in the mammalian olfactory bulb suggests a functional role for this receptor in olfaction [9].
• Moreover, all adenosine receptor agonists: 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), A2A receptor agonist, N6-cyclopentyladenosine (CPA), A1 receptor agonist, and 5'-N-ethylcarboxamidoadenosine (NECA), A2/A1 receptor agonist significantly and dose-dependently decreased cocaine-induced locomotor activity [10].

High impact information on Adora2a

• The A2a receptor (A2aR) is abundant in basal ganglia, vasculature and platelets, and stimulates adenylyl cyclase [3].
• Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation [11].
• In vivo treatment with a low dose of CBD decreases TNFalpha production in lipopolysaccharide-treated mice; this effect is reversed with an A2A adenosine receptor antagonist and abolished in A2A receptor knockout mice [12].
• Inhibition of PKA reversed the desensitization effects of adenosine compounds, suggesting that PKA was necessary for A2a receptor-mediated heterologous desensitization [13].
• Moreover, the A2a receptor-induced cross-desensitization also reduced the susceptibility of monocytes to infection by an R5 strain of HIV-1 [13].

Chemical compound and disease context of Adora2a

• Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis [14].
• The adenosine A2A receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), significantly decreased catalepsy induced by raclopride and haloperidol, while the adenosine A1 receptor antagonist, 1,3-dimethyl-8-phenylxanthine (8-PT), was ineffective [15].
• Adenosine A2A receptor-deficient and A2A receptor antagonist-treated mice were protected from developing bleomycin-induced dermal fibrosis [16].
• In MPTP-treated monkeys, A2A receptor-blockade with an antagonist alleviates parkinsonian symptoms without provoking dyskinesia, suggesting this receptor may offer a new target for the antisymptomatic therapy of Parkinson's disease [17].
• OBJECTIVES: The purpose of this study is to examine the efficacy and potency of the novel selective adenosine A2A receptor antagonist (E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dhydro- 1H-purine-2,6- dione (KW-6002) in ameliorating the motor deficits in various mouse models of Parkinson's disease [18].

Biological context of Adora2a

• D1A2A receptor knockout mice shared phenotypic similarities with mice deficient in D1 receptors, while also paralleling behavioral deficits seen in A2A receptor knockout mice, indicating individual components of the behavioral phenotype of the D1A2A receptor knockout attributable to the loss of both receptors [19].
• Further experiments examined the effects of A2AR activation and associated vasodilation with low-flow ischemia in the absence of beta-adrenergic stimulation [1].
• We report here the characterization of a transgenic mouse model (Tg-A2aR/Tg-E7) resulting from the coexpression of two oncogenic transgenes in the thyroid [20].
• Adenosine A2A receptor gene disruption provokes marked changes in melanocortin content and pro-opiomelanocortin gene expression [21].
• Characterization of genomic organization of the adenosine A2A receptor gene by molecular and bioinformatics analyses [22].

Anatomical context of Adora2a

• An A2a receptor-specific agonist failed to enhance mast cell mediator release, which suggests that the secretory process is modulated through the A2b and/or another receptor subtype [23].
• We therefore asked whether A2AR occupancy affects macrophage foam cell formation in response to IC and the cytokine interferon-gamma [24].
• Adenosine A2A receptor (A2AR) antagonism attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration and quinolinic acid-induced excitotoxicity in the neostriatum [7].
• In confirmation of the role of A2AR in prevention of foam cell formation, CGS-21680 also inhibited foam cell formation in cultured murine peritoneal macrophages but did not affect foam cell formation in A2AR-deficient mice [24].
• In contrast the exact distribution of A2aR in other regions of the central nervous system remains unclear [9].

Associations of Adora2a with chemical compounds

• In contrast, ethanol and saccharin preference in D1A2A receptor knockout mice were distinctly different from that observed in derivative D1 or A2A receptor-deficient mice [19].
• Preference and consumption of saccharin were also reduced in D1A2A receptor knockout mice, whereas saccharin preference was similar in wild-type, D1, and A2A receptor knockout mice [19].
• This effect was prevented by the A2AR antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) [1].
• The present study specifically addresses the requirement for A2aR and/or A3R for the protective effect of inosine in 2 experimental in vivo models of inflammatory disease [4].
• Cells that had been cultured for 1 to 2 days in the presence of dexamethasone demonstrated increased amounts of A2a receptor mRNA, but no identifiable change in A2b receptor mRNA [23].

Regulatory relationships of Adora2a

• Up to 63% of the A2AR influence was estimated to be mediated through its inhibition of the A1R antiadrenergic effect, with the remainder being the direct contractile effect [1].
• The genetic ablation of the AC5 gene eliminated >80% of forskolin-induced AC activity and 85-90% of AC activity stimulated by either D1 or A2A receptor agonists in striatum [25].
• Adenosine A2A receptor occupancy stimulates expression of proteins involved in reverse cholesterol transport and inhibits foam cell formation in macrophages [24].
• A2A receptor is highly coexpressed with enkephalin and D2 receptor in striatopallidal neurons [26].
• CONCLUSION: The present findings suggest that the highly selective adenosine A2A receptor agonist (ATL-146e) prevents endotoxin-induced lethal liver injury by suppression of TNF-alpha secretion [27].

Other interactions of Adora2a

• This study investigated the A1R and A2AR function in beta-adrenergic-stimulated, isolated wild-type and A2AR knockout murine hearts [1].
• Rescue of locomotor impairment in dopamine D2 receptor-deficient mice by an adenosine A2A receptor antagonist [28].
• Methotrexate reduced exudate levels of TNF-alpha in the wild-type mice and A3 receptor knockout mice but not the A2A receptor knockout mice [14].
• They highlight the role of postsynaptic A2A receptor blockade, but leave open the possibility that antagonism of presynaptic or postsynaptic A1 receptors also contributes to DARPP-32-dependent psychomotor stimulation by caffeine [29].
• We had previously generated a transgenic mouse model in which the cAMP cascade was permanently stimulated in thyroid cells by an adenosine A2a receptor (Tg-A2aR model) [30].

Analytical, diagnostic and therapeutic context of Adora2a

• A2AR activation reduced by 5% the depression of contractile function caused by the flow reduction and also increased contractile performance over a wide range of perfusion flows [1].
• 4. The efficacy of adenosine A2A receptor antagonists in reducing immobility time in the tail suspension test was confirmed and extended in two groups of mice [31].
• RT-PCR analysis revealed presence of A3, A1 and A2b but lack of A2a receptor transcripts in MC total RNA [32].
• A single injection of CGS21680 (A2A receptor agonist), induced strong expression of zif/268 mRNA, detected by in situ hybridization, not only in striatum but also in the motor cortex of the "weaver" mutant [33].
• The effects of adenosine A1 and A2A receptor agonists and antagonists administered intraperitoneally (i.p.) and their interaction with angiotensin II (Ang II) administered intracerebroventricularly (i.c.v.) were studied in mice using the acetic acid-induced abdominal constriction test [34].

References