An endogenous opioid mechanism of acute adaptation to hypoxia.
dc.contributor.author | Mayfield, Kimberly Paige | en_US |
dc.contributor.advisor | D'Alecy, Louis | en_US |
dc.date.accessioned | 2014-02-24T16:18:34Z | |
dc.date.available | 2014-02-24T16:18:34Z | |
dc.date.issued | 1994 | en_US |
dc.identifier.other | (UMI)AAI9423263 | 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:9423263 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/103999 | |
dc.description.abstract | Prior exposure of mice to severe, intermittent hypoxia induces an increase in their survival time during subsequent lethal exposure to hypoxia. This observation is similar to other studies in which prior exposure to a stress induces tolerance to subsequent stress. It appears that the specificity of the stress is not critical to inducing tolerance leading us to a more general hypothesis that a component of the stress response is responsible for the adaptation. The stress response focused upon in this dissertation is the action of endogenous opioid peptides that function as neuromodulators in processes such as respiration, cardiovascular function, and thermoregulation. We hypothesized that severe intermittent hypoxia (hypoxic conditioning) increases tolerance to hypoxia by activating endogenous opioid receptors. Initial findings of this dissertation research showed that acute adaptation to hypoxia was blocked with the opioid antagonist naloxone. Subsequent pharmacological characterization of the adaptation, using selective agonists and antagonists of the different opioid receptor types, indicated the involvement of delta receptors (and possibly the delta-1 subtype). The delta antagonists, BNTX and NTI, both blocked the adaptation thus indicating that delta receptor activation was necessary for this adaptation. Complementing this, a delta agonist, DPDPE, mimicked the adaptation indicating that delta receptor activation was sufficient for this adaptation to occur. In addition, we have explored the contribution of more traditional mechanisms of adaptation to hypoxia in this response such as increased hematocrit, de novo protein synthesis, and decreased thermal set point. Increased hematocrit and de novo protein synthesis did not appear to be major contributors to the adaptation. However, the hypoxic conditioning induced an opioid-mediated decrease in thermal set point. Thus, one mechanism by which this acute adaptation to hypoxia occurs is an opioid-mediated pathway, predominantly dependent upon activation of delta receptors, that causes a decrease in thermal set point which could lower metabolism and oxygen demand to increase survival time during hypoxia. | en_US |
dc.format.extent | 156 p. | en_US |
dc.subject | Health Sciences, Pharmacology | en_US |
dc.subject | Biology, Animal Physiology | en_US |
dc.title | An endogenous opioid mechanism of acute adaptation to hypoxia. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Physiology | 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/2027.42/103999/1/9423263.pdf | |
dc.description.filedescription | Description of 9423263.pdf : Restricted to UM users only. | en_US |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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