NOCICEPTIN ORPHANIN FQ STIMULATES EXTRACELLULAR ACIDIFICATION AND DESENSITIZATION OF THE RESPONSE INVOLVES PROTEIN-KINASE-C

A Chinese hamster ovary (CHO) cell line, CHO-ORL1, stably expressing h uman opioid receptor-like receptor 1 (ORL1) has been used to determine ORL1-mediated signaling events using microphysiometry. Nociceptin/orp hanin FQ (N/OFQ), a specific endogenous agonist of ORL1, induced an in crease in extracellular acidification rate (ECAR) in CHO-ORL1 cells, T he ECAR response stimulated by N/OFQ was concentration-dependent and p ertussis toxin-sensitive. Repeated exposures of the cells to N/OFQ cau sed desensitization of ORL1, The ECAR response was recovered at the ha lf-life of approximately 12 min after the initial challenge. Pretreatm ent with inhibitor of cAMP-dependent kinase did not affect desensitiza tion of ORL1. However, specific inhibitors for protein kinase C almost abolished N/OFQ-induced desensitization of extracellular acidificatio n responsiveness, indicating the involvement of protein kinase C in th e process, (C) 1997 Federation of European Biochemical Societies.