The present study was done to determine whether the muscle nicotinic acetylcholine receptor (nAChR) function and expression could be regulated by two different factors: (a) thymopoietin (TPO)$ sp *$, a nicotinic antagonist and (b) MyoD, a myogenic transcription factor. / Exposure of rat neonatal muscle cells in culture to TPO on a long-term (days) and short-term (minutes) basis resulted in the inhibition of $ sp{125}$I-$ alpha$-bungarotoxin (BGT) binding. Short-term pretreatment with TPO also led to a decrease in carbachol-stimulated $ sp{22}$Na uptake; however, long-term exposure resulted in an enhanced carbachol-stimulated uptake. Chronic treatment also resulted in greater muscle cell morphological development. These results suggest that TPO regulates the nAChR and exerts trophic effects on myotube morphology. / As another approach to study factors that affect nAChR expression, non-muscle cells were transfected with MyoD cDNA. After transfection, saturable, high affinity $ sp{125}$I-$ alpha$-BGT binding was readily detectable, as was carbachol-stimulated $ sp{22}$Na uptake. Both these parameters developed in parallel over time and were inhibited by nicotinic antagonists. These results suggest that the transfection of a non-muscle cell line with MyoD cDNA results in the expression, at the cell surface, of a functional muscle-type nAChR. / This work shows that the nAChR function and expression can be regulated through (a) the chronic interaction of TPO at the nAChR at the cell surface and (b) the action of MyoD at the gene level. ftn$ sp *$ As stated in the addendum to this thesis, recent work by Quik et al. 1993a has shown that the preparation presumed to be TPO, contained $ alpha$-cobratoxin; the effects observed in the present thesis must therefore now be attributed to the presence of $ alpha$-cobratoxin contaminant.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.68233 |
| Date | January 1993 |
| Creators | Odeh, Rula S. |
| 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 and Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001397888, proquestno: AAIMM94491, Theses scanned by UMI/ProQuest. |
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