Disease relevance of Adora1

• This study evaluated modulating effects of adenosine A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) and mitochondrial KATP channel blocker 5HD (5-hydroxydecanoate) on the development of tolerance to focal cerebral ischemia in rats [1].
• Pre-treatment with the adenosine A1 receptor antagonist DPCPX (1 mg/kg i.v.) prevented the inhibitory effect of GR79236 (10 microg/kg i.v.) on neurogenic vasodilation as well as GR79236-induced bradycardia and hypotension [2].
• The raised protein level of adenosine A1 receptor by ischemia was reversed to normal level after reperfusion [3].
• 1. In anaesthetized rats we tested responses evoked by systemic hypoxia (breathing 8% O2 for 5 min) and adenosine (i.a. infusion for 5 min) before and after administration of a selective adenosine A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine), or a selective adenosine A2A receptor antagonist ZM 241385 [4].
• The hippocampal extracellular 5-HT level was not affected by administration of APNEA alone, but was decreased by this agent when the adenosine A1 receptor was blocked, irrespective of whether the adenosine A2 receptor was functional [5].

Psychiatry related information on Adora1

• Adenosine A1 receptor agonist GR79236 suppresses apnea during all sleep stages in the rat [6].
• These data are consistent with adenosine A1 receptor agonist actions on REM sleep mediated through inhibition of cAMP [7].
• Adenosine A1 receptor-dependent G-protein activity in the rat brain during prolonged wakefulness [8].
• Therefore, it seems that selective adenosine A1 receptor agonists may have some attenuating influence on the development of amphetamine dependence [9].

High impact information on Adora1

• Adenosine activity was manipulated by microperfusing nephrons with adenosine A1 receptor blocker, A1-agonist, or 5'-nucleotidase inhibitor [10].
• Neutrophil infiltration into dermal inflammatory sites was signficantly reduced by adenosine A1 receptor agonists injected through intrathecal catheters [11].
• The decrease in ectosolic and cytosolic 5'-nucleotidase activity was inhibited by 8-phenyltheophylline and pertussis toxin, and was mimicked by N6-cyclohexyladenosine, an adenosine A1 receptor agonist [12].
• Activation of adenosine A1-receptor pathway induces edema formation in the pancreas of rats [13].
• CONCLUSIONS: Activation of the adenosine A1-receptor pathway may have an important role in the pathogenesis of acute pancreatitis [13].

Chemical compound and disease context of Adora1

• When the adenosine A1 receptor was blocked by CPT, the hippocampal extracellular 5-HT level was increased by adenosine, CGS-21680, and PD-125944, and decreased by caffeine, DMPX, and APNEA [5].
• 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 [14].
• CONCLUSIONS: The adenosine A1 receptor mediates the paradoxic bradycardia reflex during inferior vena cava occlusion in the face of isoproterenol via vagal afferents [15].
• Ischemic preconditioning and glucose metabolism during low-flow ischemia: role of the adenosine A1 receptor [16].
• This effect was reversed by either the selective adenosine A1 receptor antagonist, 8-cyclopentyltheophylline (IC50 = 50.3 +/- 19.9 nM) or overnight incubation with Pertussis toxin (100 ng/ml) [17].

Biological context of Adora1

• Pregnant rats were treated daily with 1 g/L of caffeine or theophylline in their drinking water during pregnancy and the effect of these methylxanthines on adenosine A1 receptor was assayed using binding and reverse transcription polymerase chain reaction (RT-PCR) assays in brains from both mothers and full-term fetuses [18].
• These results suggest that maternal caffeine or theophylline intake modulates adenosine A1 receptor, causing a down-regulation of adenosine A1 receptor in brain in both mothers and fetuses [18].
• These data suggest that the gene expression of adenosine A1 receptor was increased by ischemia probably due to the compensative response of brain [3].
• 2. Intraperitoneal (i.p.) injections of the adenosine A1 receptor agonist CPA led to dose-dependent decreases in both blood pressure and heart rate [19].
• Inhibition of glycolysis and enhanced mechanical function of working rat hearts as a result of adenosine A1 receptor stimulation during reperfusion following ischaemia [20].

Anatomical context of Adora1

• Study of an adenosine A1 receptor agonist on trigeminally evoked dural blood vessel dilation in the anaesthetized rat [2].
• The mRNA level of adenosine A1 receptor in cerebral cortex was markedly raised by this artificial ischemia [3].
• In this study we evaluated the adenosine A1 receptor-mediated effect of valerian extract (Ze 911) on postsynaptic potentials (PSPs) in pyramidal cells of the rat cingulate cortex in a slice preparation [21].
• In an attempt to know the role of adenosine A1 receptor in cerebral ischemia, the present study employed the ligation of bilateral carotid arteries to induce ischemia in Wistar rats [3].
• Adenosine A1 receptor distribution in the nucleus tractus solitarii of normotensive and spontaneously hypertensive rats [22].

Associations of Adora1 with chemical compounds

• Characterization of adenosine-A1 receptor-mediated antilipolysis in rats by tissue microdialysis, 1H-spectroscopy, and glucose clamp studies [23].
• Adenosine A1 receptor down-regulation in mothers and fetal brain after caffeine and theophylline treatments to pregnant rats [18].
• The objective of the present study was to assess quantitatively recovery after chronic theophylline administration, the effects of weaning from the drug, and the effects of the drug on adenosine A1 receptor mRNA expression in adult rats subjected to a C2 hemisection [24].
• To help determine if adenosine might play a role in the control of orexin neurons, immunohistochemistry was used to characterize the distribution of adenosine A1 receptor protein on the orexinergic neurons [25].
• The CPA (10 microM)-induced inhibition was antagonized by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 microM), an adenosine A1 receptor antagonist [21].

Physical interactions of Adora1

• Its inotropic action was almost completely abolished by pretreatment of atria with adenosine deaminase and correlated well with its binding ability to the cardiac adenosine A1 receptor [26].

Regulatory relationships of Adora1

• 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 [27].
• Adenosine A1 receptor agonists block the neuropathological changes in rat retrosplenial cortex after administration of the NMDA receptor antagonist dizocilpine [28].
• A parallel Fos detection indicates that this discrepancy may be due to the excitatory action of the medial parabrachial nucleus at the rostral pontine level that surpasses inhibitory influence of the adenosine A1 receptor activation at the medullary level particularly in the ventrolateral reticular nucleus of the medulla [29].
• Activation of inhibitory G-proteins by the adenosine A1 receptor analogue N6-phenylisopropyladenosine at 10(-6) mol/l completely blocked NE stimulated calcitonin secretion [30].
• The adenosine A1 receptor analogue N-6 phenylisopropyl-adenosine (PIA) (10(-10)-10(-6) M) inhibits dose-dependently glucagon (10(-7) M) and rGRH (10(-7) M) stimulated cAMP formation and calcitonin secretion [31].

Other interactions of Adora1

• Role of adenosine A1 receptor in the regulation of gastrin release [32].
• The post-ATP facilitation could be prevented by the adenosine A1 receptor antagonists 8-phenyltheophylline or 1,3-dipropyl-8-cyclopentyltheophylline (50 nM), or superfusion of adenosine deaminase [33].
• These results indicate that adenosine A1 receptor delayed PC in rats is mediated by MAPK-dependent mechanisms, but this phenomenon is not associated with the early or late expression of iNOS [34].
• Of particular interest, parallel up-regulation in protein and mRNA was found for the adenosine A1 receptor in the accumbens core, neuroglycan C in the accumbens shell, and the GluR5 glutamate receptor subtype in dorsal prefrontal cortex [35].
• Delayed adenosine A1 receptor preconditioning in rat myocardium is MAPK dependent but iNOS independent [34].

Analytical, diagnostic and therapeutic context of Adora1

• Adenosine A1 receptor mRNA expression in the phrenic nucleus was assessed with in situ hybridization and immunohistochemistry [24].
• This change was also observed at the protein level using Western blot analysis of adenosine A1 receptor [3].
• The expression of A2a mRNA in three main areas of the hippocampus was confirmed by in situ hybridization; A2a mRNA expression was mainly localized in the pyramidal and granular cells, the same hippocampal regions that showed adenosine A1 receptor mRNA expression [36].
• Perfusion with 2 microM R(-)-N6-2-phenylisopropyladenosine (PIA), a selective adenosine A1 receptor agonist, did not modulate taurine release [37].
• The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was administered intramuscularly immediately after ischemic preconditioning [38].

References