ORPHANIN FQ IS A FUNCTIONAL ANTI-OPIOID PEPTIDE

The heptadecapeptide orphanin FQ has recently been shown to be the end ogenous agonist for the orphan opioid-like receptor, LC132. The molecu lar evidence that LC132 and orphanin FQ are evolutionarily related to other opioid receptors and their ligands suggests that these proteins may also play a role in modulating opiate actions. We now report that orphanin FQ (0.5 - 10 nmol), injected intracerebroventricularly in mic e, does not produce hyperalgesia as suggested previously but rather re verses opioid-mediated (i.e. naloxone-sensitive) stress-induced antino ciception in three different algesiometric assays. In addition to its antagonism of endogenous opioid antinociception, orphanin FQ dose-depe ndently (2.5 - 25 nmol) reverses systemic morphine antinociception (5 mg/kg, s.c.). Based on these data, we propose that orphanin FQ is a fu nctional anti-opioid peptide. Copyright (C) 1996 IBRO.