Disease relevance of NSC 95943

• Expression of HIV-1 in U937 cells was associated with an increased accumulation of intracellular cyclic adenosine monophosphate (cAMP); addition of the adenylate cyclase inhibitor 2',5'-dideoxyadenosine to these cells decreased intracellular cAMP levels to that of controls and restored FcgammaR-mediated phagocytosis [1].
• Both adenosine and the P site agent 2',5'-dideoxyadenosine (DDA) reversibly inhibit adenylate cyclase activity in two different preparations of the enzyme that lack the stimulatory guanine nucleotide-binding protein, G/F: plasma membranes from the cyc- variant of S49 lymphoma cells and the resolved catalytic component (C) from rabbit liver [2].
• D(1)-mediated increases in progesterone-facilitated lordosis were reduced by 2',5'-dideoxyadenosine [3].
• GLP-2 stimulated proliferation was (1) inhibited in a dose-dependent fashion by both pertussis and cholera toxin and (2) augmented by 2',5'-dideoxyadenosine [4].
• We have used two new inhibitors of adenylate cyclase, 9-(tetrahydro-2-furyl)adenine (SQ 22536) and 2',5'-dideoxyadenosine (DDA), to directly reassess the role of cAMP in PTH-stimulated osteolysis [5].

High impact information on NSC 95943

• The response was reduced when 2',5'-dideoxyadenosine was injected along with NECA into the caudate nucleus or when theorphylline was given intraperitoneally [6].
• Although 8-bromo-cAMP (cAMP) also mimicked the antimigratory effects of NO donors, the antimigratory effects of SNAP were not altered by 2',5'-dideoxyadenosine (an inhibitor of adenyl cyclase) or by (R)-p-adenosine-3',5'-cyclic phosphorothioate (an inhibitor of the cAMP-dependent protein kinase) [7].
• ACh-induced hyperpolarizations of subintimal smooth muscle in arterial strips with intact endothelium were abolished by Gap 27 and the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine but were unaffected by IBMX [8].
• An adenylate cyclase inhibitor, 2',5'-dideoxyadenosine, partially inhibited the responses to forskolin and cholera toxin. cAMP analogs mimicked the effect of forskolin, and the phosphodiesterase inhibitor theophylline enhanced the response to forskolin [9].
• In addition, 2',5'-dideoxyadenosine reduced the wild-type current to the level seen in amn, whereas it failed to further reduce the current observed in amn muscles [10].

Chemical compound and disease context of NSC 95943

• VTA infusions of 8-bromo-cAMP enhanced lordosis of naturally receptive or hormone-primed rats and hamsters and 2',5'-dideoxyadenosine decreased lordosis of oestradiol + progesterone-primed rats and hamsters [3].

Biological context of NSC 95943

• Rescue from G2A-induced apoptosis was achieved by co-expression of a G alpha(12/13)-specific inhibitor, p115RGS (regulator of G protein signaling), in combination with 2',5'-dideoxyadenosine treatment [11].
• The effects of TSH were mediated by protein kinase C (PKC), rather than protein kinase A (PKA), stimulation, because inhibition of PKC by staurosporine resulted in a decrease in VEGF production of up to 65%, whereas inhibition of the PKA signal transduction pathway (2',5'-dideoxyadenosine) resulted in only a minor decrease [12].
• Neither 2',5'-dideoxyadenosine nor compound SQ 22536 alone induced platelet aggregation [13].
• Similarly, adenosine partially reversed, but 2',5'-dideoxyadenosine (DDA) totally blocked (IC50: 540 microM), the forskolin-induced stimulation of AC activity [14].
• Moreover, the cyclic AMP/PKA-dependent up-regulation of iNOS expression mediated by PGE(2) was drawn from the inhibitory effects of 2',5'-dideoxyadenosine, KT5720 and H-89 [15].

Anatomical context of NSC 95943

• Direct measurement of [3H] guanine nucleotide release from oocyte membranes preloaded with [3H] GTP demonstrated that treatment with either progesterone or 2',5'-dideoxyadenosine slows the rate of nucleotide exchange [16].
• Naturally soluble rat germ cell adenylate cyclase was inhibited by adenosine and the adenosine analogs, 9-beta-D-arabinofuranosyl adenine (AFA) and 2',5'-dideoxyadenosine (DDA), all of which inhibited hormone-sensitive adenylate cyclases at the "P" site [17].
• The relaxant effect of luteolin was unaffected by the removal of epithelium or by the presence of propranolol (1 microM), 2',5'-dideoxyadenosine (10 microM), methylene blue (25 microM), glibenclamide (10 microM), Nomega-nitro-L-arginine (20 microM), or alpha-chymotrypsin (1 U/mL) [18].
• In addition, the inhibitory effect of 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, and methylene blue, an inhibitor of guanylate cyclase, on the neurotensin-induced relaxation of gastric smooth muscle cells were examined [19].
• Erythroid differentiation and growth inhibition of K562 cells by 2',5'-dideoxyadenosine: synergism with interferon-alpha [20].

Associations of NSC 95943 with other chemical compounds

• Adenylate cyclase activity in Xenopus oocyte membranes measured in the presence of guanyl-5'-yl imidodiphosphate and 1.5 mM Mn2+ was maximally inhibited to 57% of control by progesterone and to 89% by the P site agonists, 2',5'-dideoxyadenosine and 9-beta-d-arabinofuranosyladenine [16].
• The adenylate cyclase inhibitor 2',5'-dideoxyadenosine (DDA) at 5 x 10(-4) M effectively blocks the increased cAMP synthesis by cells treated with 10 micrograms/ml PGE1 [21].
• Moreover, the adenylate cyclase antagonist 2',5'-dideoxyadenosine prevented the increase in TH mRNA produced by each peptide [22].
• In addition, 2',5'-dideoxyadenosine did not negate the stimulatory effect of PGE2 on DNA synthesis, suggesting that PGE2 increases DNA synthesis, probably via a pathway different from the adenylate cyclase/cAMP system [23].
• Isoproterenol antagonistic effect of 2',5'-dideoxyadenosine in the isolated perfused guinea-pig heart [24].

Gene context of NSC 95943

• TSHr signal transduction was evaluated by analyzing the effect of stimulators (cholera toxin, 8-bromo-cAMP, forskolin, and 12-O-tetradecanoyl-phorbol-13-acetate) and inhibitors (2',5'-dideoxyadenosine and staurosporine) on VEGF protein levels under basal and TSH-stimulated conditions [12].
• PGE(2) induction of OSM gene expression is inhibited by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine, by the protein kinase A (PKA) inhibitor H-89, and by a dominant-negative PKA construct [25].
• The suppressed ability of the tumor cell motility by VIP (10(-6) M) was practically recovered by co-treatment with 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor [26].
• Exposure of NK cells to the AC inhibitor 2',5'-dideoxyadenosine (DDA) significantly increased the total level of PLCgamma1 by 67% after 60 min and the level of p44/42 by about 30% [27].
• The adenylyl cyclase inhibitor, 2',5'-dideoxyadenosine, had no effect on ET-1-stimulated lipolysis [28].

References