FUNCTIONAL COUPLING OF THE NOCICEPTIN ORPHANIN FQ RECEPTOR WITH THE G-PROTEIN-ACTIVATED K+ (GIRK) CHANNEL/

Nociceptin/orphanin FQ is a heptadecapeptide which was recently isolat ed from brains. It induces hyperalgesia, in contrast to the analgesic effects of opioid ligands, although it and its receptor structurally r esemble opioid peptides and opioid receptors, respectively. To investi gate the molecular mechanism underlying nociceptin/orphanin FQ actions , we performed Xenopus oocyte expression assays, in situ hybridization histochemistry and electrophysiological analyses of neurons. We found that the nociceptin/orphanin FQ receptor is functionally coupled with the G-protein-activated K+ (GIRK) channel in Xenopus oocytes, and tha t the receptor mRNA and GIRK1 mRNA co-exist in various neurons, includ ing hippocampal pyramidal cells. Furthermore, we found that nociceptin /orphanin FQ induces hyperpolarizing currents via inward-rectifier Kchannels in hippocampal pyramidal cells, suggesting that the nocicepti n/orphanin FQ receptor couples with the GIRK channel in this region. W e conclude that the nociceptin/orphanin FQ receptor couples with the G IRK channel in various neurons, including hippocampal pyramidal cells, thereby modulating neuronal excitability.