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.
D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018847:Opioid Peptides / Q000494:pharmacology; D011149:Pons / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism*; D011957:Receptors, Opioid / Q000235:genetics* / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019204:GTP-Binding Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007527:Isoenzymes; D018847:Opioid Peptides; D011493:Protein Kinase C; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C087857:protein kinase C gamma; C000722287:Oprl1 protein, mouse