The present experiments were carried out to test the hypothesis that NC is involved in nicotinic receptor mediated muscle cell degeneration. As a model to study nicotinic receptor mediated myopathy, neonatal skeletal muscle cultures prepared from one day old Sprague-Dawley pups were used. Skeletal muscle cultures were exposed to different concentrations of nicotine. The results demonstrate a significant dose dependent decrease in the number of muscle branch points with increasing nicotine concentrations. The degenerative effect(s) of nicotine were prevented by preincubating the muscle cultures with d-tubocurarine, a nicotinic receptor blocker, suggesting that the effects of nicotine are receptor mediated. Experiments were then done to assess an involvement of the NO generating system in the nicotine induced degeneration. NO synthase (NOS) inhibitors prevented/inhibited the nicotine induced degenerative effects on myotube size and branching, while exposure of the cells to sodium nitroprusside (SNP), an agent which releases NO spontaneously, resulted in myotube degeneration. As another approach to determine an involvement of NO in the myopathy, the effect of nicotine on NOS activity was determined. NOS activity increased in a time and tissue dependent manner in neonatal rat skeletal muscle cultures. NOS activity was then determined in the absence or presence of nicotine. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27310 |
| Date | January 1997 |
| Creators | El-Dada, Manar. |
| Contributors | Quik, Maryka (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001565222, proquestno: MQ29685, Theses scanned by UMI/ProQuest. |
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