Orphanin FQ has an inhibitory effect on the guinea pig ileum and the mouse vas deferens

The activity of the recently isolated endogenous opioid-like peptide orphanin FQ (OFQ) was measured in two classical bioassays of opioid action. OFQ potently and concentration-dependently suppressed the electrically stimulated contractions of the guinea pig ileum (GPI) and the mouse vas deferens (MVD)) with EC₅₀ values of 1.82 ± 0.16 and 2.97 ± 0.01 mM, and E(max) values of 56 ± 3% and 96 ± 4%, respectively. This effect of OFQ, in both the GPI and MVD, was insensitive to the opioid receptor antagonist naloxone. OFQ competed with [³H]diprenorphine binding to μ-, δ or κ- opioid receptors stably expressed in Chinese hamster ovary cell lines with IC₅₀ values of 2.1 ± 0.4, 2.2 ± 0.3, 0.75 ± 0.3 μM, respectively. Low affinity for the classical opioid receptors together with the inability of naloxone to antagonize its effect suggest that the inhibitory action of OFQ is mediated via a distinct OFQ receptor in the GPI and MVD. Consequently, the MVD could serve as a valuable bioassay of potential OFQ receptor antagonists.