Abstract
The aim of the present study was to investigate whether repeated treatment with the μ-opioid receptor antagonist naloxone could affect G-protein activation induced by a selective μ-opioid receptor agonist [ d-Ala 2, N-MePhe 4,Gly-ol 5]enkephalin (DAMGO) in mice lacking the protein kinase Cγ isoform monitoring guanosine-5’- o-(3-[ 35S]thio)triphosphate ([ 35S]GTPγS) binding. Repeated s.c. administration of naloxone for 7 days resulted in a significant enhancement of the increased [ 35S]GTPγS binding by DAMGO to membranes of the spinal cord obtained from mice lacking the protein kinase Cγ isoform. Furthermore, immunoreactivities of membrane-located protein kinase Cγ and phosphorylated-protein kinase C in the spinal cord of ICR mice were not altered by repeated naloxone treatment. The present data provide direct evidence that protein kinase Cγ is not involved in the development of the up-regulation of μ-opioid receptor functions to activate G-proteins in the mouse spinal cord by repeated naloxone treatment.
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