REGULATION OF KAPPA OPIOID RECEPTORS

Project: Research project

Project Details

Description

DESCRIPTION: (Applicant's Abstract)

The exposure of an opioid receptor to opioid peptides or opiate alkaloids
initiates a biological response. A long-term or repeated exposure to
opioids causes a decreased sensitivity to the drug, leading to a reduced
cellular response; this desensitization is regulated by multiple mechanisms
which have been implicated in the generalized development of tolerance and
addiction. Acute opioid treatments result in a rapid desensitization by
functional uncoupling of the receptor from the effector system. In
addition, this treatment results in a rapid internalization of the receptor
into intracellular compartments. Chronic opioid treatment results in longer
desensitization due to receptor down-regulation with a net loss of binding
sites from the cell. Relatively little is known about the molecular
mechanisms underlying these events. The objective of the studies proposed
here is to explore the agonist-mediated events that lead to receptor
internalization and degradation. These studies propose to explore the
molecular mechanisms of opioid receptor internalization and dimerization in
order to understand the functional significance of these events. The
specific aims are: (i) to characterize kappa opioid receptor trafficking in
neuronal cells, and (ii) to explore the role of dimerization in kappa opioid
receptor function. This work will provide critical information about the
early agonist-mediated events that modulate opioid receptor function. A
thorough understanding of the cellular mechanisms involved in the modulation
of receptor desensitization is crucial for the development of a therapeutic
basis for drug addiction.
StatusFinished
Effective start/end date9/1/988/31/99

Funding

  • NATIONAL INSTITUTE ON DRUG ABUSE

ASJC

  • Biological Psychiatry
  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Cell Biology
  • Pharmacology

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