Orphanin FQ/Nociceptin

Orphanin FQ (nociceptin, OFQ), a heptadecapeptide peptide, has been designated as an endogenous ligand for the ORL1 receptor. The amino acid sequence of OFQ has homology with other opioid peptides, especially the prodynorphin fragment  dynorphin A, suggesting a close evolutionary relationship between the precursors. A diffuse distribution throughout the brain is seen with binding studies and in situ hybridization suggesting an extensive role for OFQ in a multitude of CNS functions. Immunocytochemical localizations in rat spinal cord have demonstrated OFQ abundance in superficial dorsal horn, lateral spinal nucleus and the region dorsal to the central canal. OFQ immunoreactivity was not affected by dorsal rhizotomy, indicating that in spinal cord the peptide is produced by central rather than primary afferent neurons. The localization is supported by its function in processing of nociceptive signals.

Note: Peptide sequence corresponds to: amino acids 135-151 of rat, 154-170 of mouse and 130-146 of human pro-nociceptin.

Image: Confocal images showing OFQ (red), GnRH (green) and their colocalization (yellow) in the ovine preoptic area and hypothalamus.

A-C: Low power view of the preoptic area at the level of the organum vasculosum of the lamina terminalis (OVLT) showing OFQ and GnRH cells, and their colocalization (e.g., white arrows). Bar = 100µm. D-F: High power images of a double-labeled OFQ/GnRH cell; note that the immunofluorescence for OFQ has a punctateappearance in the cytoplasm as opposed to the more diffuse appearance of the GnRH signal. Bar 26 = 20µm. G-I: Single-labeled OFQ cells (e.g., red arrow) in the arcuate nucleus. Note that many GnRH fibers coursing through this region are also OFQ-positive (e.g., white arrows). 3v = third ventricle. Bar = 100µm. Endocrinology. First published ahead of print July 5, 2007 as doi:10.1210/en.2007-0011