The nociceptor/orphanin FQ peptide and its homologous receptor encoded by the Oprl1 gene represent the recently discovered opioid peptide/receptor system NOPR, which is a G protein coupled receptor with 60% sequence similarity to other members of the opioid drug family, while retaining unique pharmacological features. After being occupied by its endogenous peptide ligand N/OFQ, the receptor activates downstream Gi/Go proteins and induces intracellular signaling, including inhibiting cAMP formation, and ultimately reduces neurotransmission by inhibiting voltage-gated calcium channels and activating inward rectifying potassium channels.

It is worth noting that previous studies on N/OFQ signal transduction have yielded some contradictory results. It has been reported that activating NOPR with selective agonists can reduce alcohol consumption and seeking behavior, while the selective NOPR antagonist LY2940094 has been reported to have the same effect. Overall, the exact mechanism of the NOPR-N/OFQ system and its impact on different neural circuits can only be partially understood.

The research team reported on the development and characterization of NOPLight, a gene encoded opioid peptide sensor that provides specificity and sensitive fluorescence readings for endogenous N/OFQ kinetics, with high temporal resolution in vitro and in vivo. The research team also measured the chemical and behavioral induction kinetics of endogenous N/OFQ in freely moving mice. NOPLight extends the neuropeptide molecular toolbox required for studying neuropeptide physiology, particularly the high-resolution of this important endogenous opioid drug system.

Source: Sensor Expert Network