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)

Previous studies have shown that nicotinic cholinergic agonists induce muscle cell degeneration. Although an involvement of calcium is well documented, subsequent intracellular steps have not been identified. The present experiments test whether nitric oxide (NO) may play such a role. Both the irreversible nitric oxide synthase inhibitor L-5N-iminoethyl ornithine and L-nitroarginine methyl ester, a reversible inhibitor, protected the muscle cells from the myopathic effects of nicotine. These results may suggest that nicotinic receptor stimulation produces an increase in NO that results in muscle cell degeneration. In line with this interpretation, exposure of the muscle cultures to the NO donor sodium nitroprusside resulted in a dose-dependent decline in myotube branch points. Neither L-5N-iminoethyl ornithine nor nitroprusside altered the binding of the nicotinic receptor agonist 125I-alpha-bungarotoxin to muscle cells in culture, which indicates that the effect of these agents was not mediated through an interaction at the nicotinic receptor recognition site. The results with agents that inhibit guanylate cyclase or modify extracellular levels of cGMP suggest an involvement of this cyclic nucleotide in the nicotinic receptor-mediated myopathy. To conclude, the present results suggest that nicotinic receptor activation causes skeletal muscle degeneration through an increase in NO production and a possible involvement of cGMP.
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PMID:Involvement of nitric oxide in nicotinic receptor-mediated myopathy. 919 Aug 84

Duchenne muscular dystrophy (DMD), a severe X-linked recessive disorder which results in progressive muscle degeneration, is due to a lack of dystrophin, a membrane cytoskeletal protein. An approach to treatment is to compensate for dystrophin loss with utrophin, another cytoskeletal protein with over 80% homology with dystrophin. Utrophin is expressed, at the neuromuscular junction, in normal and DMD muscles and there is evidence that it may perform the same cellular functions as dystrophin. So, the identification of molecules or drugs that could up-regulate utrophin is a very important goal for therapy. We show that in adult normal and mdx mice (an animal model of Duchenne myopathy) treated with l-arginine, the substrate of nitric oxide synthase (NOS), a pool of utrophin localized at the membrane appeared and increased, respectively. In normal and mdx myotubes in culture, l-arginine, nitric oxide (NO), or hydroxyurea increased utrophin levels and enhanced its membrane localization. This effect did not occur with d-arginine, showing the involvement of NOS in this process. The NO-induced increase in utrophin was prevented by oxadiazolo-quinoxalin-1-one, an inhibitor of a soluble guanylate cyclase implicated in NO effects. These results open the way to a potential treatment for Duchenne and Becker dystrophies.
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PMID:Nitric oxide and l-arginine cause an accumulation of utrophin at the sarcolemma: a possible compensation for dystrophin loss in Duchenne muscular dystrophy. 1060 Apr 5