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 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.
Pei
G
G
Shanghai Institute of Cell Biology, Chinese Academy of Sciences, People's Republic of China.
Ling
K
K
Pu
L
L
Cunningham
M D
MD
Ma
L
L
D000818:Animals; D015152:Blotting, Northern; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D015342:DNA Probes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D015870:Gene Expression; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018847:Opioid Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011957:Receptors, Opioid / Q000819:agonists / Q000235:genetics / Q000502:physiology; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000097629:Nociceptin
D000242:Cyclic AMP; D015342:DNA Probes; D004791:Enzyme Inhibitors; D019204:GTP-Binding Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018847:Opioid Peptides; D037342:Pertussis Toxin; D011493:Protein Kinase C; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D000097629:Nociceptin