NOCICEPTIN ORPHANIN FQ ACTIVATES PROTEIN-KINASE-C, AND THIS EFFECT ISMEDIATED THROUGH PHOSPHOLIPASE C/CA2+ PATHWAY/

The effect of nociceptin/orphanin FQ (N/OFQ) on protein kinase C (PKC) was investigated in Chinese hamster ovary cells stably expressing opi oid receptorlike (ORL1) receptor (CHO-ORL1 cells). N/OFQ significantly activated PKC in CHO-ORL1 cells with EC50 of 0.2 nM. This response wa s blocked by PKC inhibitors chelerythrine and Go 6976, and by pretreat ment of cells with pertussis toxin (PTX). The inhibition of PKC activa tion by N/OFQ was also achieved by use of Ca2+-chelators and phospholi pase C (PLC) inhibitor U-73122. These results indicate that N/OFQ can effectively activate PKC via ORL1 receptor, and suggest the activation involve the PLC/Ca2+ system. (C) 1997 Academic Press.