Nociceptin receptor-mediated Ca2+ channel inhibition and its desensitization in NG108-15 cells.
It has been shown that the membrane of hybrid NG108-15 neuroblastoma x glioma cells contains a high-affinity binding site for nociceptin. In the present study, we first demonstrated the expression of nociceptin receptor mRNA in NG108-15 cells. Application of nociceptin to NG108-15 cells produced a concentration-dependent (EC50 = 29 nM) inhibition of Ca2+ channel currents in a pertussis toxin-sensitive fashion. This nociceptin-induced inhibition of Ca2+ channel currents was prevented in the presence of omega-conotoxin GVIA, a blocker of the N-type Ca2+ channel, and had both voltage-dependent and -independent components. Prolonged application of nociceptin elicited homologous desensitization of the inhibition with a time constant of 5.3 min. These results indicate that the nociceptin receptor is coupled to the N-type Ca2+ channel via pertussis toxin-sensitive G proteins in NG108-15 cells and that this coupling is associated with rapid and homologous desensitization.
Department of Anesthesia, Kyoto University Hospital, Japan. kin@kuhp.kyoto-u.ac.jp
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Morikawa
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Fukuda
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Mima
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Shoda
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Kato
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Mori
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D015342:DNA Probes; D019204:GTP-Binding Proteins / Q000378:metabolism; D006822:Hybrid Cells; D051379:Mice; D018847:Opioid Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D015220:Calcium Channels; D015342:DNA Probes; D019204:GTP-Binding Proteins; D018847:Opioid Peptides; D012333:RNA, Messenger; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin