Influence of a deletion of protein kinase C gamma isoform in the G-protein activation mediated through opioid receptor-like-1 and mu-opioid receptors in the mouse pons/medulla.

The aim of the present study was to investigate whether mice with a deletion of the gene that encodes the protein kinase C gamma (PKC gamma) isoform could affect the G-protein activation mediated through the opioid receptor-like (ORL-1) receptor and mu-opioid receptor in the mouse pons/medulla and spinal cord, monitoring the guanosine-5'-o-(3-[(35)S]thio) triphosphate ([(35)S]GTP gamma S) binding assay. The increases in [(35)S]GTP gamma S bindings to pons/medulla membranes of the wild-type mice induced by either an endogenous ligand for the ORL-1 receptor, nociceptin or a selective mu-opioid receptor agonist [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin were significantly enhanced in PKC gamma knockout mice. In contrast, the levels of [(35)S]GTP gamma S binding stimulated by nociceptin in spinal cord membranes obtained from PKC gamma knockout mice were similar to those from wild-type mice. These findings suggest that the loss of the PKC gamma gene may protect the functional ORL-1 and mu-opioid receptors from degradation by phosphorylation in the mouse pons/medulla. Furthermore, the present data provide first evidence for the differential mechanism of the ORL-1 receptor-mediated signaling between the supraspinal and spinal sites.