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Up-regulation of spinal μ-opioid receptor function to activate G-protein by chronic naloxone treatment

Authors
Journal
Brain Research
0006-8993
Publisher
Elsevier
Publication Date
Volume
913
Issue
2
Identifiers
DOI: 10.1016/s0006-8993(01)02785-8
Keywords
  • μ-Opioid Receptor
  • Up-Regulation
  • Naloxone
  • G-Proteins
  • [35S]GtpγS Binding
  • Spinal Cord
Disciplines
  • Biology

Abstract

Abstract The effects of repeated s.c. administrations of an μ-opioid receptor antagonist naloxone on the G-protein activation induced by μ-opioid receptor agonists [ d-Ala 2, N-MePhe 4,Gly-ol 5]enkephalin (DAMGO), endomorphin-1 and endomorphin-2 in the mouse spinal cord was studied, monitoring guanosine-5′- o-(3-[ 35S]thio)triphosphate ([ 35S]GTPγS) binding. All μ-opioid receptor agonists concentration-dependently increased the [ 35S]GTPγS binding. The increases of [ 35S]GTPγS binding induced by agonists were significantly enhanced in mice pretreated with naloxone. Under the present condition, chronic treatment with naloxone significantly increased the density of [ 3H]DAMGO binding sites with an increase in K d values in spinal cord membranes, indicating an increase in μ-opioid receptors on the membrane surface. These findings suggest that chronic treatment with an μ-opioid receptor antagonist naloxone leads to the supersensitivity to activate G-protein by μ-opioid receptor agonists with an increase in μ-opioid receptors in membranes of the mouse spinal cord.

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