ATTENUATION OF NOCICEPTIN ORPHANIN FQ-INDUCED SIGNALING BY N-METHYL-D-ASPARTATE IN NEURONAL CELLS/

ACUTE incubation of NMDA with neuroblastoma x glioma hybrid (NG108-15) cells or neuroblastoma SK-N-SH cells produced significant attenuation of nociceptin/orphanin FQ (N/OFQ)-induced activation of G protein and inhibition of adenylyl cyclase. The attenuation of N/OFQ signaling by NMDA was dose-dependent, blockable by NMDA antagonists, and not obser ved in cells lacking NMDA receptors, indicating that the effect of NMD A is mediated by the NMDA receptor. Furthermore, NMDA antagonist pretr eatment greatly attenuated N/OFQ-induced acute homologous desensitizat ion of ORL1. Interestingly, the signaling induced by etorphine, an opi oid agonist of wide spectrum, was sensitive to NMDA treatment in NG108 -15 but insensitive in SK-N-SH cells, suggesting differential modulati on of opioid signaling by NMDA. The attenuation effects of NMDA on mu opioid receptor-mediated signaling were also observed.