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Vol. 289, Issue 2, 607-624, May 1999
Department of Pharmacology, University of Minnesota Medical School,
Minneapolis, Minnesota
From the demonstration of the existence of multiple opioid receptors
and the isolation of the endogenous opioid peptides in the brain, it is
now clear that the activities of these receptors can be regulated at
various levels. The distinct brain regional distribution of the
receptor suggests a tight transcriptional regulation. Early findings of
alterations in receptor binding associated with tolerance to the
opioids implies that the receptor life cycle can be influenced by the
presence of agonists. Until the recent reported cloning of opioid
receptors, the detailed studies of the molecular mechanisms involved in
their regulation could not be conducted. With the availability of the
cDNA clones of the µ-, 
- and 
-opioid receptors, and the
elucidation of their gene structures, it is now possible to investigate
opioid receptor regulation at various levels, and to identify the
specific receptors involved in the pharmacological actions of the
opioids. It is now also possible to define the receptor domains
responsible for the opioid ligand selectivities, agonist activation,
and agonist-induced inactivation. Summarized in this report are our
past efforts in defining the regulation of opioid receptor activities.
Studies using heterologous expression techniques, mutational analysis of receptors to characterize transcriptional elements, and the in vivo
manipulation of the receptor gene levels have made it is possible to
determine the mechanisms whereby these receptors are regulated. Our
studies have also identified the unique characteristics of opioid
receptors as members of the superfamily of G protein-coupled receptors.
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