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Title: Molecular mechanisms of agonist-induced trafficking of the μ-opioid receptor
Author: Cooke, Alexandra Eleanor
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2013
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Mu-opioid receptor (MOPr) agonists such as morphine are amongst the most important therapies for the acute relief of moderate to severe pain. However, their clinical efficacy is often compromised due to considerable inter-individual variability, the associated side effects and the development of tolerance and dependence. Numerous molecular mechanisms have been proposed to mediate tolerance to opioids. Although a definitive mechanism remains to be elucidated, desensitization, internalization and resensitization of the MOPr have all been repeatedly implicated as contributing factors. Like most G protein-coupled receptors (GPCRs), MOPr activity is tightly regulated by rapid desensitization and resensitization in response to activation by high efficacy opioid agonists. In contrast, morphine is typically reported to induce little or no acute desensitization or internalization. Howev~r, repeated or chronic administration of morphine results in considerable tolerance that is often greater than that induced by highly efficacious opioids. Despite intensive research into the regulation of the MOPr at the molecular, cellular and systems levels, much still remains to be learned about the mechanisms that underlie tolerance to opioids. The aim of this thesis was to investigate agonist-induced MOPr trafficking at the molecular and cellular level and its relationship to cellular morphine tolerance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available