Elsevier

Neuroscience

Volume 75, Issue 2, 25 October 1996, Pages 333-337
Neuroscience

Letter to Neuroscience
Orphanin FQ is a functional anti-opioid peptide

https://doi.org/10.1016/0306-4522(96)00338-7Get rights and content

Abstract

The heptadecapeptide orphanin FQ has recently been shown to be the endogenous agonist for the orphan opioid-like receptor, LC132. The molecular 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 mice, does not produce hyperalgesia as suggested previously but rather reverses opioid-mediated (i.e. naloxone-sensitive) stress-induced antinociception in three different algesiometric assays. In addition to its antagonism of endogenous opioid antinociception, orphanin FQ also dose-dependently (2.5–25 nmol) reverses systemic morphine antinociception (5 mg/kg, s.c.).

Based on these data, we propose that orphanin FQ is a functional anti-opioid peptide.

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Acknowledgements

We thank Drs Malcolm J. Low, Richard H. Goodman, John T. Williams, Antonello Bonci and Nicholas J. Grahame for helpful comments on this manuscript, and Ge Zhang for sharing data with us prior to publication. This work was supported by NINDS (J.S.M.), NIAAA (J.E.G.), NIDA and the Markey Charitable Trust (D.K.G.), and the U.S. Veterans Administration (J.K.B.).

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