Disease relevance of 8 BrGuo

• BACKGROUND AND METHODS: In this study, we investigated the effect of 8-bromoguanosine (8Brguo), an immunostimulatory compound, in a murine model of experimental cutaneous leishmaniasis [1].
• Using an experimental model of porcine liver ischemia, 8-bromoguanosine 3',5' monophosphate, a cGMP analog, was continuously administered into the portal vein before ischemia and after reperfusion 30 min for each in the cGMP group (n = 6) [2].

High impact information on 8 BrGuo

• Furthermore, 8-bromoguanosine 3':5'-cyclic monophosphate and sodium nitroprusside inhibited lipocyte contractility, consistent with the effect of NO induced by cytokines [3].
• These data (i) indicate that, by interaction with cellular components, 8-BrGuo triggers high level lymphocyte activation and (ii) cast significant doubt on the role of cGMP as an intracellular second messenger in lymphocyte proliferation [4].
• Although authentic NO.induces a rapid increase in cGMP levels in hepatocytes, the addition of the cGMP analog 8-bromoguanosine 3':5' cyclic monophosphate to unstimulated HC cultures does not reproduce the inhibition of total protein synthesis [5].
• An analogue of cGMP, 8-bromoguanosine 3':5'-cyclic monophosphate (cGMP), can shift the phase of the circadian rhythm from the eye; the phase response curves for light and for 8-bromo cGMP are indistinguishable [6].
• Forskolin and 8-bromoguanosine 3'-5'-cyclic monophosphate (8-Br-cGMP) induce phosphorylation of Ser-13 of telokin and relaxation of smooth muscle at constant calcium [7].

Biological context of 8 BrGuo

• Moreover, at equimolar concentrations, underivatized cGMP actually antagonized the induction of antibody production by 8BrGuo [8].
• Activation of B cells with 8- bromoguanosine ( 8BrGuo ), an intracellular mitogen, did not result in protein rearrangement until 12 hr after mitogen addition, suggesting that initial stages of signal transduction by 8BrGuo and LPS follow separate pathways [9].
• Folding thermodynamics and kinetics of YNMG RNA hairpins: specific incorporation of 8-bromoguanosine leads to stabilization by enhancement of the folding rate [10].
• Migratory capacity of C3L5 cells was reduced after treatment with the guanylate cyclase (GC) inhibitor 1-H-[1,2,4]oxadiaxolo[4,3-a]quinolalin-1-one (ODQ) and restored in the additional presence of 8-bromoguanosine 3'5'-cyclic monophosphate (8-Br cGMP, cGMP analogue), demonstrating a pivotal role for GC in C3L5 cell migration [11].
• The observed enhancement of B-lymphocyte activation by 8-bromoguanosine and 8-mercaptoguanosine is hypothesized to occur via a "binding protein" which requires a guanine nucleoside as the syn conformer for productive interaction [12].

Anatomical context of 8 BrGuo

• Direct comparisons were undertaken to determine whether this activity is exerted only by virtue of the structural resemblance of 8-BrGuo to 8-bromo cyclic GMP (8-BrcGMP) (a known intracellular lymphocyte mitogen) [4].
• Active transformation of tolerogenic to immunogenic signals in T and B cells by 8-bromoguanosine [13].
• Furthermore, elimination of asialo-Gm-1+ cells reduced the responses of NK and macrophages to 8-BrGuo, indicating that these cells possibly produce the IFN [14].
• Similarly, preincubation of peptone-elicited peritoneal macrophages with 8-BrGuo induced macrophage cytolytic activity to P815 cells in an 18-h assay [14].
• Activation of murine natural killer cells and macrophages by 8-bromoguanosine [14].

Associations of 8 BrGuo with other chemical compounds

• Lymphokine-like activity and selective stimulation of B cell growth is exerted by a group of synthetic ribonucleosides derivatized at C8 and exemplified by 8-bromoguanosine (8BrGuo), 8-mercaptoguanosine, and 7-methyl 8-oxoguanosine [15].
• IL 1 mimics lipopolysaccharide and 8-bromoguanosine, which generate IL 1 production, in its ability to interfere with the in vivo induction of tolerance [16].
• Methylene blue inhibited the ability of 8-bromoguanosine 3',5'-monophosphoric acid to promote smooth muscle relaxation, suggesting that it also may impair the subsequent actions of cyclic GMP [17].
• Since ANP is known to increase the level of cGMP it was also investigated whether 8-bromoguanosine 3':5' cyclic monophosphate, a permeable cGMP analog, displaced diazepam binding [18].
• 5-Halo-6-phenyl pyrimidinones, represented by 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) and 2-amino-5-iodo-6-phenyl-4(3H)-pyrimidinone (AIPP), and 8-substituted guanosines, represented by 8-bromoguanosine (8-BrGuo) and 8-mercaptoguanosine (8-MGuo), are well-documented biological response modifiers [19].

Gene context of 8 BrGuo

• Direct enzymatic phosphorylation does not seem to be essential to the mechanism of action of the nucleoside insofar as competitive inhibition of deoxycytidine kinase (an enzyme that directly phosphorylates purines as well as pyrimidines) or of deoxyguanosine kinase fails to inhibit 8BrGuo stimulation selectively [15].
• The studies reported in this communication demonstrate that, in contrast to naturally occurring nucleosides, 8BrGuo is not a substrate for salvage by purine nucleoside phosphorylase [15].
• ABPP, AIPP, 8-BrGuo, and 8-MGuo induced murine B cells to polyclonally proliferate and differentiate in vitro [19].
• These data, together with the recent observations that 8-BrGuo, like ABPP and AIPP, can stimulate NK and cytotoxic macrophage activity via the induction of interferon, strongly suggest that 5-halo-6-phenyl pyrimidinones and 8-substituted guanosines belong to the same structural class of biological response modifiers [19].
• Alternatively, a series of guanosine analogs prepared in our laboratories, 8-bromoguanosine, 8-mercaptoguanosine, 7-methyl-8-oxoguanosine and 7-thia-8-oxoguanosine, all activate various aspects of the immune response by up-regulation of G protein regulatory pathways in various lymphocyte derived cells [20].

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