Disease relevance of Adora3

• A selective A2A receptor agonist (CGS-21680), an adenosine A2 receptor agonist (PD-125944), an adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and an adenosine A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA), did not affect extracellular 5-HT levels [1].
• Activation of the adenosine A3 receptor subtype by the agonist N6-2-(4-aminophenyl)ethyladenosine is shown here to induce bronchospasm (increased pulmonary resistance and decreased pulmonary compliance) in BDE strain rats [2].
• The recently cloned G protein-coupled adenosine A3 receptor has been proposed to play a role in the pathophysiology of cerebral ischemia [3].
• A role for mast cells in adenosine A3 receptor-mediated hypotension in the rat [4].
• Effect of pertussis toxin treatment on the putative adenosine A3 receptor-mediated hypotensive response in the rat [5].

High impact information on Adora3

• We have characterized the actions of a selective adenosine A3 receptor agonist, 2-chloro-N6-(3-lodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA), and a selective A3 receptor antagonist, 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS 1191), in brain slices from rat hippocampus [6].
• Oral epinastine blocked bronchospasm (increase in RL) in BDE rats induced by the adenosine A3 receptor agonist N6-2-(4-aminophenyl)ethyladenosine with an ED50 of only 0.47 mg/kg [7].
• An adenosine receptor distinct from A1 and A2 receptors has been cloned from testis and designated TGPCR, or A3, although it differs from the pharmacologically defined A3 receptor [8].
• Resveratrol-mediated activation of cAMP response element-binding protein through adenosine A3 receptor by Akt-dependent and -independent pathways [9].
• The mechanism by which activation of the adenosine A3 receptor induces bronchospasm is distinct from the mechanism by which activation of the adenosine A1 receptor induces bronchospasm [2].

Chemical compound and disease context of Adora3

• N6-Cyclopentyladenosine (CPA, adenosine A1 receptor agonist) and 5'-N-ethylcarboxamidoadenosine (NECA, adenosine A1/A2 receptor agonist) reduced, while N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA, non-selective adenosine A3 receptor agonist) did not alter sympathetic activity [10].
• Xanthine insensitivity, high potencies of APNEA, NECA and R-PIA, and an enantiomeric selectivity favouring R- over S-PIA are distinguishing features of the adenosine A3 receptor [11].
• The cardiovascular effects of N6-2-(4-aminophenyl)ethyladenosine (APNEA), which when radiolabelled with 125I shows high affinity for the newly described adenosine A3 receptor, have been investigated in the angiotensin II-supported circulation of the pithed rat [11].
• Adenosine A3 receptor activation produces nociceptive behaviour and edema by release of histamine and 5-hydroxytryptamine [12].
• Antigen-induced mediator release (beta-hexosaminidase and [3H]5-hydroxytryptamine) was increased by APNEA, an adenosine A3 receptor agonist (EC50 approximately 20 nm) but inhibited by EHNA and 5-IT, despite increased adenosine levels [13].

Biological context of Adora3

• The observation of rapid tachyphylaxis in combination with histamine release suggests that mast cell mediator release plays a key role in the hemodynamic effects of adenosine A3 receptor agonists [14].
• Roles of BCL-2 and caspase 3 in the adenosine A3 receptor-induced apoptosis [15].
• To determine whether adenosine A3 receptor stimulation produces airway inflammation and, if so, what the mechanism of action is, we studied microvascular permeability in the rat trachea [16].

Anatomical context of Adora3

• In vivo role of the adenosine A3 receptor: N6-2-(4-aminophenyl)ethyladenosine induces bronchospasm in BDE rats by a neurally mediated mechanism involving cells resembling mast cells [2].
• The adenosine antagonist, 8-phenyltheophylline (8-PT) (10 microM), abolished the inhibitory effects of NECA (100 nM-100 microM) on 10, 15 and 25 day old rat duodenum indicating that the responses to NECA were not mediated via an adenosine A3 receptor [17].

Associations of Adora3 with chemical compounds

• 1. Adenosine receptor agonists were evaluated for their activity at the putative adenosine A3 receptor which mediates a 'xanthine-resistant' hypotensive response in the anaesthetized rat [18].
• Species-dependent hemodynamic effects of adenosine A3-receptor agonists IB-MECA and Cl-IB-MECA [19].
• Hemodynamic effects and histamine release elicited by the selective adenosine A3 receptor agonist 2-Cl-IB-MECA in conscious rats [14].
• The hemodynamic effects of the novel, selective adenosine A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (2-Cl-IB-MECA) were investigated in conscious rats [14].
• This study evaluated the pain enhancing properties of the adenosine A3 receptor agonist N6-benzyl-5'-N-ethylcarboxamidoadenosine (N6-benzyl-NECA) by assessing behavioural effects following s.c. administration alone to the dorsal hindpaw of the rat, or in combination with a low concentration of formalin (0.5%) [12].

Other interactions of Adora3

• These results illustrate that adenosine A3-receptor agonists produce species-dependent effects, which in the rat heart appear to be caused by adenosine A2a-receptor activation [19].

Analytical, diagnostic and therapeutic context of Adora3

• BACKGROUND: The cardioprotective effects of the adenosine A3 receptor in a cardioplegia model have not been described [20].
• In the present study, the effect of adenosine A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA), on methamphetamine (MTH)-induced dopamine (DA) release in rat striatum was evaluated using microdialysis in freely moving animals [21].

References