Enhanced μ-Opioid Responses in the Spinal Cord of Mice Lacking Protein Kinase Cγ Isoform

Document Type

Article

Publication Date

5-4-2001

Description

The protein kinase C (PKC)γ isoform is a major pool of the PKC family in the mammalian spinal cord. PKCγ is distributed strategically in the superficial layers of the dorsal horn and, thus, may serve as an important biochemical substrate in sensory signal processing including pain. Here we report that μ-opioid receptor-mediated analgesia/antinociception and activation of G-proteins in the spinal cord are enhanced in PKCγ knockout mice. In contrast, δ- and κ-opioidergic and ORL-1 receptor-mediated activation of G-proteins in PKCγ knockout mice was not altered significantly relative to the wild-type mice. Deletion of PKCγ had no significant effect on the mRNA product of spinal μ-opioid receptors but caused an increase of maximal binding of the μ-opioid receptor agonist [ 3H][D-Ala2,N-Me-Phe4,Gly5-ol] enkephalin in spinal cord membranes obtained from PKCγ knockout mice. These findings suggest that deletion of PKCγ genes protects the functional μ-opioid receptors from degradation by phosphorylation. More importantly the present data provide direct evidence that PKCγ constitutes an essential pathway through which phosphorylation of μ-opioid receptors occurs.

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