Opioid receptor binding and signal transduction: Modulation by the plasma membrane.
dc.contributor.author | Emmerson, Paul Joseph | en_US |
dc.contributor.advisor | Medzihradsky, Fedor | en_US |
dc.contributor.advisor | Hollenberg, Paul | en_US |
dc.date.accessioned | 2014-02-24T16:23:35Z | |
dc.date.available | 2014-02-24T16:23:35Z | |
dc.date.issued | 1995 | en_US |
dc.identifier.other | (UMI)AAI9610115 | en_US |
dc.identifier.uri | http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9610115 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/104769 | |
dc.description.abstract | Information in the form of chemical signals crosses the cellular plasma membrane by binding to integral membrane proteins initiating a signaling cascade. The organization of the lipid bilayer, its complex composition as well as its diverse biophysical properties, has been shown to modulate the function of integral membrane proteins. The purpose of this research was to examine the potential regulatory role of the plasma membrane in mu opioid receptor binding and signal transduction. Addition of cholesteryl hemisuccinate (CHS) rigidified the membranes from the human neuroblastoma cell line SH-SY5Y resulting in increased opioid agonist binding and reduced modulation by sodium and guanine nucleotide without affecting the binding of opioid antagonists. In membranes in which G protein was reduced or inactivated, addition of CHS resulted in the conversion of agonist binding to a single state suggesting that increased microviscosity favors the formation of a G protein independent form of the receptor. In the absence of a G protein, rigidification of the membrane no longer reduced the inhibitory effects of sodium on agonist binding suggesting that the reduction of these effects in control membranes may involve the stabilization of the receptor-G protein interaction. Further examination of opioid agonist signal transduction utilized agonist stimulation of guanosine-$\rm5\sp\prime$O-(3-$\rm\lbrack \sp{35}S\rbrack$thio)triphosphate binding to G protein. The efficacy of agonists at the cloned rat mu opioid receptor stably expressed in $\rm C\sb 6$ glioma cells was reflected in the magnitude of the stimulation of this nucleotide. The effects of CHS on opioid agonist binding and agonist signal transduction in this system suggested a differential modulation of opioid ligands dependent upon ligand efficacy. The further study of these protein-lipid interactions will be aided by the development of a series of fluorescent opioid ligands. These ligands maintain high affinity for the mu opioid receptor and possess a highly fluorescent label which was used to specifically label the cloned mu opioid receptor expressed in $\rm C\sb 6$ glioma cells. The research presented in this thesis highlights the regulatory role for the lipid bilayer in opioid signal transduction mechanisms. | en_US |
dc.format.extent | 134 p. | en_US |
dc.subject | Health Sciences, Pharmacology | en_US |
dc.title | Opioid receptor binding and signal transduction: Modulation by the plasma membrane. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Pharmacology | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/104769/1/9610115.pdf | |
dc.description.filedescription | Description of 9610115.pdf : Restricted to UM users only. | en_US |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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