Disease relevance of ADORA1

• Despite significant progress in understanding of the potential of adenosine A1 receptor-based therapies in treatment of cerebral ischemia and stroke, very little is known about the effect of selective stimulation of adenosine A2A receptors on the outcome of a cerebrovascular arrest [1].
• In contrast, the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (100 nM), did not significantly modify the extracellular accumulation of either glutamate or aspartate caused by inducers of chemical ischemia or glycolytic inhibitors [2].
• Adenosine modulates cell proliferation in human colonic adenocarcinoma. I. Possible involvement of adenosine A1 receptor subtypes in HT29 cells [3].
• Dysregulation of adenosine A1 receptor-mediated cytokine expression in peripheral blood mononuclear cells from multiple sclerosis patients [4].
• Blockade of adenosine A1 receptor signal transduction with the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine or with pertussis toxin pretreatment increased both basal and dopamine-stimulated cAMP levels, indicating the existence of tonic adenosine A1 receptor activation [5].

Psychiatry related information on ADORA1

• Recent evidence indicates that a cascade of signal transduction induced by basal forebrain adenosine A1 receptor activation in cholinergic neurons leads to increased transcription of the A1 receptor; this may play a role in mediating the longer-term effects of sleep deprivation, often called sleep debt [6].
• Adenosine A1 receptor and bipolar affective disorder: systematic screening of the gene and association studies [7].
• Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine A1 receptor agonist [8].
• Modified electroconvulsive shock can induce rapid tolerance associated with adenosine A1 receptor activation subjected to focal cerebral ischemia in rats [9].

High impact information on ADORA1

• Administration of an aerosolized phosphorothioate antisense oligodeoxynucleotide targeting the adenosine A1 receptor desensitized the animals to subsequent challenge with either adenosine or dust-mite allergen [10].
• The adenosine A1 receptor is assumed to reside in presynaptic terminals and to function as a negative autoreceptor [11].
• An increase in the PR interval and atrial natriuretic peptide level, consistent with adenosine A1 receptor-mediated activity, was observed [12].
• BACKGROUND: The role of adenosine as a neuromodulator in heart failure was studied with the use of a selective adenosine A1 receptor agonist, N6-cyclohexyl-2'-O-methyladenosine (SDZ-WAG 994) [12].
• VT recurred with the addition of aminophylline, a competitive adenosine A1-receptor antagonist [13].

Chemical compound and disease context of ADORA1

• The adenosine A1 receptor antagonist DPCPX did not affect the resting hyperventilation of 1-7CH rats breathing 12% O2 and increased resting heart rate (HR) in 1CH rats only [14].
• 5. The response to histamine (0.1 mM) was not altered by prior treatment of cells with pertussis toxin (100 ng ml-1; 24 h) whereas the inositol phosphate response to adenosine A1-receptor stimulation in this cell line was significantly attenuated under these conditions [15].
• CONCLUSIONS: In vitro, desflurane preconditions human myocardium against simulated ischemia through activation of mitochondrial K(ATP) channels, adenosine A1 receptor, and alpha and beta adrenoceptors [16].
• In the present study the selective adenosine A1 receptor agonist N6-cyclopentyladenosine stimulated a pertussis toxin-sensitive increase in total [3H]inositol phosphate accumulation [17].
• This was blocked by treatment of cells with pertussis toxin or the adenosine A1 receptor selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine [18].

Biological context of ADORA1

• Several lines of experimental evidence suggest that an excess of adenosine A1 receptor activity may contribute to adiposity in NIDDM [19].
• Using monoclonal anti-adenosine A1 receptor antibodies that bind the A1 receptor ligand binding site, we demonstrate that A1 receptors are expressed on cultured monocytes and rheumatoid synovial fluid mononuclear phagocytes [20].
• Localization of the adenosine A1 receptor subtype gene (ADORA1) to chromosome 1q32.1 [21].
• Using the sequence conservation in the G protein-coupled receptor superfamily, we have isolated an adenosine A1 receptor cDNA from a human hippocampal cDNA library by homology screening [22].
• AICA riboside also depressed excitatory synaptic transmission in area CA1 of the rat hippocampus, which was prevented by an adenosine A1 receptor antagonist and reversed by application of adenosine deaminase [23].

Anatomical context of ADORA1

• This finding is associated with the acquisition of reactivity with selective adenosine A1 receptor agonists and is temporally coordinated with the induction of adenosine A2 receptors on cultured monocytes [20].
• The affinity of adenosine for the human adenosine A1 receptor expressed on Chinese hamster ovary cell membranes has been measured in the presence and absence of GTP [24].
• Overexpressing the adenosine A1 receptor also led to increased protection against ischemia-induced myocyte injury as well as an enhanced preconditioning effect [25].
• Diminished adenosine A1 receptor expression on macrophages in brain and blood of patients with multiple sclerosis [26].
• Adenosine A1 receptor (A1R) immunoreactivity was found in degenerating neurons with neurofibrillary tangles and in dystrophic neurites of senile plaques [27].

Associations of ADORA1 with chemical compounds

• The directly acting adenosine A1 receptor agonists are known to mediate neuroprotection, mostly by the blockade of Ca2+ influx, which results in the inhibition of glutamate release and reduction of its excitatory effects at a postsynaptic level [28].
• The release of [3H]ACh evoked by 50 mM KCl was mostly Ca2+ dependent, and it was increased in the presence of adenosine deaminase and in the presence of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A1 receptor antagonist [29].
• Options for acute treatment based on preclinical work and initial clinical studies include: serotonin 5HT1F and 5HT1D receptor agonists, glutamate excitatory amino acid receptor antagonists, nitric oxide synthase inhibitors and adenosine A1 receptor agonists [30].
• By using luminol-enhanced chemiluminescence, we found that adenosine A1 receptor activation did not affect, whereas adenosine A receptor activation, through a mechanism involving the cyclic AMP (cAMP)-protein kinase A signalling pathway, both inhibited the fMLP- and IgG-triggered respiratory burst [31].
• In membrane preparations, both the adenosine A1 receptor agonist N6-cyclopentyladenosine and the GTP analogue guanyl-5'-yl imidodiphospate induced a decrease in the proportion of dopamine D1 receptors in a high affinity state [5].

Regulatory relationships of ADORA1

• The presence of ADA may promote the signaling through the adenosine A1 receptor in HEK293 cells [32].
• The effect of Gi coupled receptor activation (adenosine A1 and 5-HT1B receptors) on cholecystokinin receptor-stimulated inositol phosphate accumulation has been investigated in Chinese hamster ovary cells transfected with the human adenosine A1 receptor cDNA (CHO-A1) [17].
• This appeared to be mediated by a pathway initiated at the adenosine A1 receptor that transduced signals through a Ca2+-activated Cl- channel and EGFR [33].
• Previously, we have reported that the adenosine A1 receptor (A1AR) regulates tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expression and exhibits diminished function in patients with multiple sclerosis (MS; Mayne et al., Ann Neurol 1999;45:633-639) [26].
• Adenosine A1 receptor analogues also inhibit TRH-stimulated [Ca2+]i-mobilization in GH3 cells [34].

Other interactions of ADORA1

• DESIGN: Case-control association study investigating gene variants for the ADORA1, ADORA2a and ADA genes [35].
• Also, stimulation of adenosine A1 receptor-coupled Galpha(16) was shown to induce ERK and STAT1 phosphorylations in a concentration-dependent manner [36].
• Moreover, we found upregulation of the proto-oncogene SKI and of receptors for neuromediators such as opioid mu1 receptor, GABA B receptor, adenosine A1 receptor, orexin 1 and 2 receptors and corticotropine-releasing hormone receptor [37].
• Human adenosine A1 receptor and P2Y2-purinoceptor-mediated activation of the mitogen-activated protein kinase cascade in transfected CHO cells [38].
• The stable adenosine A1 receptor agonist N6-phenylisopropyl adenosine (PIA) was also totally devoid of effect on the spontaneous or ACTH-induced release of corticosteroids [39].

Analytical, diagnostic and therapeutic context of ADORA1

• In the present study, we investigate the distribution of the adenosine A1 receptor in the rat spinal cord dorsal horn using immunohistochemistry, in situ hybridization, radioligand binding, and confocal microscopy [40].
• Adenosine A1 receptor agonists and metabolic inhibitors, e.g. of transport, deaminase and xanthine oxidase have been demonstrated to be effective in different animal models of ischemia [41].
• A selective adenosine A1 receptor antagonist attenuates renal dysfunction during controlled hypotension with adenosine in rats [42].
• Chronological changes of adenosine A1 receptor binding of the rat brain were determined by in vitro [3H]cyclohexyladenosine (CHA) autoradiography after 90 min of middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation [43].
• While ischemic preconditioning involves the activation of the adenosine A1 receptor, the bradykinin receptor, and activation of adenosine triphosphate (ATP)-dependent potassium channels, the mechanisms underlying myocardial hibernation are still unclear [44].

References