Disease relevance of 2 Chloroadenosine

• Inability of anti-asialo-GM1 and 2-chloroadenosine to abrogate maleic anhydride-divinyl ether-induced resistance against experimental murine lung carcinoma metastases [1].
• Neuroblastoma adenylate cyclase. Role of 2-chloroadenosine, prostaglandin E1, and guanine nucleotides in regulation of activity [2].
• 2-Chloroadenosine (0.6 mg/kg, IV) was administered 5 min subsequent to ischemia [3].
• Effect of 2-chloroadenosine on cerebrovascular reactivity to hypercapnia in newborn pig [4].
• Pertussis toxin pretreatment suppressed all the effects induced by 2-chloroadenosine [5].

Psychiatry related information on 2 Chloroadenosine

• We found that incubation of the ileum with adenosine, or with the more potent derivative, 2-chloroadenosine, induced a novel form of drug dependence, made manifest by withdrawal of inducing drug, but not by antagonists of opiates or clonidine [6].
• In conclusion, 2-chloroadenosine not only acts as an anticonvulsant against electrically induced kindled seizures as described here, and against audiogenic seizures, electroshock and a variety of chemical convulsants as described by others, it prevents the development of the epileptic state by kindling-stimulation, i.e., it is antiepileptogenic [7].
• Moreover, the influence of the adenosine antagonist on 2-chloroadenosine (1 mg/kg, 20 min prior to the test)- and valproate (250 mg/kg, 30 min)-induced inhibitions of locomotor activity was also studied [8].

High impact information on 2 Chloroadenosine

• The finding that 2-chloroadenosine, which is not metabolized, resembled adenosine in its ability to inhibit superoxide anion generation added further evidence that adenosine metabolism was not required for inhibition of superoxide anion generation by neutrophils [9].
• Since adenosine and its analogue 2-chloroadenosine prevent neutrophils from generating superoxide anion in response to chemoattractants, we sought to determine whether these agents could inhibit neutrophil-mediated injury of endothelial cells [10].
• In addition, drug action can be blocked by exogenous agonists such as 2-chloroadenosine and also can be antagonized by removal of endogenous agonists by treatment with adenosine deaminase [11].
• Adenosine or 2-chloroadenosine caused a slow hyperpolarization of the membrane potential and, under voltage clamp, an outward current that was blocked by 1 mM theophylline [12].
• Taxol also antagonized the enhancement of cAMP increases by colchicine in lymphocytes stimulated by 2-chloroadenosine, isoproterenol, and cholera toxin [13].

Chemical compound and disease context of 2 Chloroadenosine

• 3. Of these agents, NECA was observed to exhibit the greatest intrinsic activity, while in comparison maximal responses to adenosine (76+/-8% NECA response), 2-chloroadenosine (70+/-6%) and APNEA (40+/-3%) were significantly reduced [14].
• Prostaglandin E2 and 2-chloroadenosine act in concert to stimulate bone resorption in cultured murine calvarial bones [15].
• These data suggest that 2-chloroadenosine can induce bone resorption by a mechanism independent of stimulation of prostaglandin synthesis but that the amount of 2-chloroadenosine stimulated resorption is enhanced by endogenous and exogenous PGE2 [15].
• After systemic administration of SKF-38393 or L-dopa, central microinjection of the adenosine agonists, 2-chloroadenosine or 5'-N-ethylcarboxamide adenosine, were effective in preventing self mutilation induced by these dopamine agonists in neonatally lesioned rats [16].
• Adenosine and the analogues, 5'-(N-ethylcarboxamido)adenosine (NECA), R-N6-phenylisopropyladenosine (R-PIA), 2-chloroadenosine, N6-2-(4-aminophenyl)ethyladenosine (APNEA) and 5'-AMP yielded bronchoconstrictor responses as increases in perfusion pressure or of tension, respectively, of these two preparations [17].

Biological context of 2 Chloroadenosine

• 2-Chloroadenosine (5 x 10(-4) M) caused a 29% phosphorylation of Protein I, and this effect was not dependent on extracellular Ca2+ [18].
• Exposure of cultured neutrophils to 2-chloroadenosine or 5'-N-ethylcarboxamidoadenosine (NECA) decreased apoptosis after 16 h, with half-maximal responses for NECA and 2-chloroadenosine of 7.1 +/- 7.7 and 59.0 +/- 32.0 nM, respectively [19].
• This affinity and the observation that 2-chloroadenosine and 5'-N-ethylcarboxamidadenosine are the most potent inhibitors of phagocytosis suggest that the Ado receptors expressed during monocyte differentiation are of the A2 type [20].
• Exposure to 1.0 microM 2-chloroadenosine induced a significant (11.1 +/- 3.2%) reduction in vessel diameter, whereas a 100 microM concentration induced an afferent vasodilation (7.6 +/- 1.5%; p less than 0.05) [21].
• Growth-arrested SMC were treated with 2.5% FCS in the presence and absence of adenosine, 2-chloroadenosine, or 8-bromo-cAMP for 24 hours for DNA synthesis or 4 days for cell proliferation [22].

Anatomical context of 2 Chloroadenosine

• Depletion of macrophages from the adherent cells by 2-chloroadenosine or silica abrogated the production of this cytotoxic activity, whereas treatment of the adherent cells with anti-Thy-1.2 antibody and complement did not [23].
• In the present study, we attempted to utilize anti-asialo-GM1 antibody and 2-chloroadenosine, agents that kill natural killer (NK) cells and macrophages, respectively, to determine the relative contribution of each effector cell type to the overall host defense [1].
• Compounds like 2-chloroadenosine and carbocyclic adenosine are extremely efficient inactivators of the isolated enzyme, but these nucleosides exerted only a limited effect on the enzyme in intact hepatocytes [24].
• Treatment of Caco-2 cells with 2ClAdo prevented ST-induced increases in [cGMP]i, chloride current and water secretion [25].
• We investigated the ability of adenosine and its stable analogue 2-chloroadenosine (CADO) to inhibit cytokine production and cytotoxic activity of lymphokine-activated killer (LAK) cells and determined whether both these effects are initiated via a common pathway [26].

Associations of 2 Chloroadenosine with other chemical compounds

• Furthermore, with vehicle treatment, both baseline BF and reactivity to endothelium-dependent (acetylcholine) and endothelium-independent (2-chloroadenosine) vasodilators were significantly depressed after 24 hours of reperfusion [27].
• The half-maximally effective agonist concentrations were approximately 75 nM for somatostatin, approximately 100 nM for serotonin, and approximately 400 nM for 2-chloroadenosine [28].
• We find that similar dose-dependent inhibitory effects can be induced by each of four other agents that raise cAMP levels in such cells: forskolin, PGE2, 2-chloroadenosine, and isoproterenol [29].
• The general nature of the FMLP-potentiated cAMP response is indicated by the finding that FMLP-treated neutrophils, in the presence of exogenously supplied adenosine deaminase, exhibited augmented cAMP generation in response to three different types of receptor agonists: 2-chloroadenosine, prostaglandin E1, and L-isoproterenol [30].
• In our studies on the effects of purine compounds on immune responses in vitro, we found that 2-chloroadenosine (2-Cl Ado) exhibited a potent lethal effect on a viability of mouse adherent cells derived from the peritoneal cavity [31].

Gene context of 2 Chloroadenosine

• Bradycardia and vasodilation in response to AR agonism (2-chloroadenosine) were unaltered by ADA deficiency, while A1AR deficiency eliminated the heart rate response [32].
• Stimulation of BAECs with tumor necrosis factor-alpha or transforming growth factor-beta increased ET-1 synthesis, and treatment of BAECs with 2-chloroadenosine or staurosporine caused concentration-dependent reductions in ET-1 synthesis [33].
• Cyst formation and expansion were inhibited by TGF beta 1 and 2-chloroadenosine [34].
• 2. Exposing cells for 24 h to 2-chloroadenosine (2-CADO), a nonspecific, adenosine deaminase (ADA)-resistant, adenosine receptor (AdoR) agonist, induced DNA fragmentation, and thus apoptosis, in RA-FLSs at concentrations > or =50 microM [35].
• Pre-treatment with a selective A1AR agonist (50 nM CHA) failed to modify coronary dysfunction, whereas A1AR antagonism (200 nM DPCPX) worsened the effects of I/R (2-chloroadenosine pEC50=6.9+/-0.1) [36].

Analytical, diagnostic and therapeutic context of 2 Chloroadenosine

• Perfusion with 0.1 mmol/L 2-chloroadenosine attenuated basal as well as NMDA-enhanced [14C]L-citrulline recovery [37].
• Pericardial 2-chloroadenosine caused more uniform distribution of radiotracer microspheres than intravascular 2-chloroadenosine [38].
• Ligation of adenosine receptors by a receptor agonist, 2-chloroadenosine (2CADO), enhanced iNOS mRNA expression by both HGEC and transformed HGEC [39].
• Despite this difference, the 2-chloroadenosine infusion induced similar hemodynamic changes (clearances of inulin and p-aminohippurate, filtration fraction) in the two kidneys [40].
• However, doses of naloxone (i.t.) that antagonized analgesia induced by i.t. injections of morphine had no effect on 2-chloroadenosine (i.t.)-induced analgesia [41].

References