Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium nitroprusside (SNP) stimulates cGMP formation to a greater extent in 20,000 g supernatant fractions of the human neuroblastoma clones NB1-G and SH-SY5Y than in the human astrocytoma clone D384. This suggests that these cell lines contain the soluble form of guanylate cyclase. Arachidonic, 8,11,14- and 11,14,17-eicosatrienoic acids inhibit SNP (10(-4) M)-stimulated cGMP formation more potently than the C18 unsaturated fatty acids linolenic and linoleic acids in D384 and NB1-G. In contrast the C20 saturated fatty acid, arachidic acid had little effect even at 10(-4) M concentration. In addition arachidonic and 8,11,14-eicosatrienoic acids inhibited basal guanylate cyclase activity, in NB1-G, over the same concentration range as they inhibited SNP-stimulated cGMP formation. No evidence could be obtained for the stimulation of guanylate cyclase by arachidonic acid in either NB1-G or D384. These results provide further support for suggestions that arachidonic acid or its metabolites may be important regulators of cGMP formation in the nervous system.
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PMID:The effect of unsaturated fatty acids on sodium nitroprusside stimulation of guanylate cyclase in the human astrocytoma clone, D384, and the human neuroblastoma clone, NB1-G. 196 40

The role of the L-arginine-NO pathway on the formation of PGE2 by cultured astroglial cells incubated with the HIV coating glycoprotein gp120 was investigated. Preincubation of human cultured T 67 astrocytoma cells with gp 120 (100-500 nM) produced a significant increase of nitrite (the breakdown product of NO) and PGE2 in cell supernatants. The effect of gp 120 on both nitrite and PGE2 production was antagonized by inhibition of NO synthase by L-NAME (20-300 microM). The inhibition of gp120-induced PGE2 production by L-NAME was reverted by addition of arachidonic acid (30 microM), an effect antagonized by the cyclo-oxygenase inhibitor indomethacin (10 microM). Methylen bleu, an inhibitor of the biological activity of NO acting at the guanylate cyclase level failed to affect gp 120-mediated PGE2 release showing that the increase of cGMP subsequent to NO production was not involved in the modulatory activity of NO on arachidonic acid cascade. On the basis of present experiments we conclude that gp-120-induced release of PGE2 by astroglial cells is driven by NO, thereby contributing in the involvement of glial cells in HIV-related cerebral disorders.
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PMID:HIV coating gp 120 glycoprotein-dependent prostaglandin E2 release by human cultured astrocytoma cells is regulated by nitric oxide formation. 752 Nov 67

The effect of 6-anilino-5,8-quinolinedione (LY83583), an inhibitor of guanylyl cyclase (GC), on the growth of human brain tumor cells (U-373 MG astrocytoma and SK-N-MC neuroblastoma) was evaluated. LY83583 inhibited the growth of these cells in a dose-dependent manner. This growth inhibition was found to be the result of decreased cell viability as assessed by the trypan blue exclusion method. The LY83583-induced decrease in cell viability was not altered by dibutyryl cyclic GMP, but significantly was reversed by superoxide dismutase and catalase, indicating that these effects of LY83583 may not be due to the inhibition of GC, but due to the formation of superoxide anion. The LY83583-induced decrease in cell viability was potentiated by cotreatment with sodium nitroprusside (SNP), a nitric oxide (NO) donor. This SNP-induced potentiation was significantly blocked by various scavengers for hydroxyl radicals or by intracellular Ca2+ release blockers. These results suggest that the potentiation effects of SNP may be mediated through the generation of hydroxyl radicals which can be formed by the interaction of superoxide anion (from LY83583) and NO (from SNP), and that intracellular Ca2+ release from internal stores may play an important role in the cytotoxic mechanism of hydroxyl radicals.
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PMID:Mechanism of potentiation of LY83583-induced growth inhibition by sodium nitroprusside in human brain tumor cells. 762 54

The effects of interferon gamma (gamma IFN) on the MHCII antigen expression by human cultured astrocytoma cells were investigated. The co-incubation of gamma IFN with T67 astrocytoma cells produced a dose-dependent increase of MHCII antigen expression as evaluated by flow cytometric (FACS) analysis and confocal laser microscopy analysis. The number of MHCII molecules expressed by gamma IFN-pretreated astrocytoma cells was reduced by co-incubation with N omega-nitro-L-arginine methyl ester (L-NAME), a selective inhibitor of the nitric oxide (NO)-synthesizing enzyme. In addition, methylene blue, which inhibits the biological activity of NO acting at the guanylate cyclase level, strongly antagonized the MHCII antigen expression on astrocytoma cells induced by gamma IFN. Furthermore, gamma IFN increased the activity of the inducible isoform of NO-synthase as well as the concentration of nitrite, one of the breakdown products of NO and the antiplatelet activity of astrocytoma cells. In conclusion, the present data show that gamma IFN increases the synthesis and release of NO by cultured astrocytoma cells and this could co-participate in the MHCII antigen expression by this cell type. Therefore, the generation of NO by cultured astrocytoma cells may represent an important step in the development of the immunocompetent activity of astrocytes.
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PMID:The generation of nitric oxide participates in gamma IFN-induced MHC class II antigen expression by cultured astrocytoma cells. 769 70

The aim of this study was to investigate the role of NO-cGMP pathway in NMDA-induced NGF mRNA expression by T67 astrocytoma cells. Levels of nitrite, a breakdown product of NO, in supernatants of NMDA-treated astrocytoma cells were significantly higher compared with control cells, this effect being reversed by the specific NO synthase inhibitor L-NAME. Furthermore, NGF mRNA expression was induced by NMDA treatment, this effect being inhibited by pretreating cells with L-NAME. Moreover, methylene blue, an inhibitor of NO biological activity at guanylate cyclase level, inhibited NMDA-induced NGF mRNA expression and this effect was reversed by dbt2-cGMP. These findings suggest that NO-cGMP pathway mediates the synthesis of NGF mRNA.
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PMID:NMDA-dependent NGF mRNA expression by human astrocytoma cells is mediated by nitric oxide. 769 84

Methylene blue (MB), a known inhibitor of guanylyl cyclase, induced cytotoxicity in SK-N-MC human neuroblastoma and U-373 MG human astrocytoma cells in a dose-dependent manner. MB did not significantly alter cellular levels of cGMP in both cells. 8-Br cGMP, a membrane-permeable analogue of cGMP, did not decrease MB-induced cytotoxicity, indicating that cGMP may not be a major target of the cytotoxic action of MB. However, hydroxyl radical scavengers or intracellular Ca2+ modulators effectively blocked the MB-induced cytotoxicity. These results suggest that hydroxyl radical and intracellular Ca2+ may have an important involvement in the cytotoxic action of MB. These results further suggest that the treatment with MB may be useful for the therapeutic applications of human brain tumors.
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PMID:Methylene blue induces cytotoxicity in human brain tumor cells. 787 86

Intracellular Ca(2+) mobilization and release into mammal CSF plays a fundamental role in the etiogenesis of fever induced by the proinflammatory cytokine interleukin-1beta (IL-1beta) and other pyrogens. The source and mechanism of IL-1beta-induced intracellular Ca(2+) mobilization was investigated using two experimental models. IL-1beta (10 ng/ml) treatment of rat striatal slices preloaded with (45)Ca(2+) elicited a delayed (30 min) and sustained increase (125-150%) in spontaneous (45)Ca(2+) release that was potentiated by l-arginine (300 microm) and counteracted by N-omega-nitro-l-arginine methyl ester (l-NAME) (1 and 3 mm). The nitric oxide (NO) donors diethylamine/NO complex (sodium salt) (0.3 and 1 mm) and spermine/NO (0.1 and 0.3 mm) mimicked the effect of IL-1beta on Ca(2+) release. IL-1beta stimulated tissue cGMP concentration, and dibutyryl cGMP enhanced Ca(2+) release. The guanyl cyclase inhibitors 1H-[1,2, 4]oxadiazole[4,3-a] quinoxalin-1-one (100 microm) and 6-[phenylamino]-5,8 quinolinedione (50 microm) counteracted Ca(2+) release induced by 2.5 but not 10 ng/ml IL-1beta. Ruthenium red (50 microm) and, to a lesser extent, heparin (3 mg/ml) antagonized IL-1beta-induced Ca(2+) release, and both compounds administered together completely abolished this response. Similar results were obtained in human astrocytoma cells in which IL-1beta elicited a delayed (30 min) increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) (402 +/- 71.2% of baseline), which was abolished by 1 mm l-NAME. These data indicate that the NO/cGMP-signaling pathway is part of the intracellular mechanism transducing IL-1beta-evoked Ca(2+) mobilization in glial and striatal cells and that the ryanodine and the inositol-(1,4,5)-trisphosphate-sensitive Ca(2+) stores are involved.
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PMID:Nitric oxide modulation of interleukin-1[beta]-evoked intracellular Ca2+ release in human astrocytoma U-373 MG cells and brain striatal slices. 1112 73