Nociceptin/orphanin FQ stimulates extracellular acidification and desensitization of the response involves protein kinase C

Abstract
A Chinese hamster ovary (CHO) cell line, CHO‐ORL1, stably expressing human opioid receptor‐like receptor 1 (ORL1) has been used to determine ORL1‐mediated signaling events using microphysiometry. Nociceptin/orphanin FQ (N/OFQ), a specific endogenous agonist of ORL1, induced an increase in extracellular acidification rate (ECAR) in CHO‐ORL1 cells. The ECAR response stimulated by N/OFQ was concentration‐dependent and pertussis toxin‐sensitive. Repeated exposures of the cells to N/OFQ caused desensitization of ORL1. The ECAR response was recovered at the half‐life of approximately 12 min after the initial challenge. Pretreatment with inhibitor of cAMP‐dependent kinase did not affect desensitization of ORL1. However, specific inhibitors for protein kinase C almost abolished N/OFQ‐induced desensitization of extracellular acidification responsiveness, indicating the involvement of protein kinase C in the process.