Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that low-dose ethanol would reduce cardiac myocyte function through increased production in the nitric oxide/cyclic GMP signal transduction pathway, rather than reduced degradation. Ventricular myocytes were isolated from the hearts of 9 rabbits. Myocyte function was studied using a video-edge detector and cyclic GMP levels were measured by radioimmunoassay. Cells were administered 5 and 10 mmol/l ethanol alone or after 10(-6) mol/l N(G)-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), 10(-6) mol/l 1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (ODQ, soluble guanylyl cyclase inhibitor) or 10(-5) mol/l zaprinast (cyclic GMP phosphodiesterase inhibitor). Ethanol (10 mmol/l) significantly decreased percent shortening from 10.0 +/- 0.9 to 6.0 +/- 0.2%. Similar decrements occurred in the maximum rate of shortening and relaxation. After L-NAME or ODQ, the decrements in percent shortening, maximum rate of shortening and relaxation caused by ethanol were not significant. After zaprinast, ethanol significantly decreased the maximum rate of shortening and relaxation and percent shortening to 4.3 +/- 0.5. Ethanol (10 mmol/l) significantly increased cyclic GMP from 403 +/- 121 to 529 +/- 128 fmol/10(5) myocytes. Both L-NAME and ODQ lowered cyclic GMP, and ethanol did not affect cyclic GMP after either. Zaprinast raised cyclic GMP, as did its combination with 10 mmol/l ethanol (653 +/- 120). Thus, ethanol both reduced myocyte function and increased cyclic GMP. Blocking nitric oxide production or guanylyl cyclase activity prevent these effects of ethanol, while blocking cyclic GMP degradation did not. This suggests that ethanol acts as a nitric oxide stimulator in ventricular myocytes leading to reduced function and increased cyclic GMP.
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PMID:Ethanol reduces cardiac myocyte function through activation of the nitric oxide-cyclic GMP pathway. 1256 49

The sporulation stage of the aquatic fungus Blastocladiella emersonii culminates with the formation and release to the medium of a number of zoospores, which are motile cells responsible for the dispersal of the fungus. The presence in the sporulation solution of 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a potent and selective inhibitor of nitric oxide-sensitive guanylyl cyclases, completely prevented biogenesis of the zoospores. In addition, this compound was able to significantly reduce cGMP levels, which increase drastically during late sporulation, suggesting the existence of a nitric oxide-dependent mechanism for cGMP synthesis. Furthermore, increased levels of nitric oxide-derived products were detected during sporulation by fluorescence assays using DAF-2 DA, whose signal was drastically reduced in the presence of the nitric oxide synthase inhibitor Nomega-Nitro-L-arginine methyl ester (L-NAME). These results were confirmed by quantitative chemiluminescent determination of the intracellular levels of nitric oxide-derived products. A putative nitric oxide synthase (NOS) activity was detected throughout sporulation, and this enzyme activity decreased significantly when L-NAME and 1-[2-(Trifluoromethyl)phenyl]imidazole (TRIM) were added to the assays. NOS assays carried out in the presence of EGTA showed decreased enzyme activity, suggesting the involvement of calcium ions in enzyme activation. Additionally, expressed sequence tags (ESTs) encoding putative guanylyl cyclases and a cGMP-phosphodiesterase were found in B. emersonii EST database (http://blasto.iq.usp.br), and the mRNA levels of the corresponding genes were observed to increase during sporulation. Altogether, data presented here revealed the presence and expression of guanylyl cyclase and cGMP phosphodiesterase genes in B. emersonii and provided evidence of a Ca(2+)-(*)NO-cGMP signaling pathway playing a role in zoospore biogenesis.
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PMID:Evidence of a Ca(2+)-(*)NO-cGMP signaling pathway controlling zoospore biogenesis in the aquatic fungus Blastocladiella emersonii. 1939 57


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