Orphanin FQ antagonizes the inhibition of Ca(2+) currents induced by mu-opioid receptors.

Orphanin FQ (OFQ), an endogenous peptide ligand of opioid receptor-like receptors (ORLs), has properties similar to traditional opioids. This peptide inhibits adenylyl cyclase and voltage-gated calcium channels but stimulates inwardly rectifying potassium channels. Among other actions, however, OFQ also has pharmacological functions that are different from, or even opposite to, those of opioids. For example, OFQ antagonizes the behavioral analgesic effects mediated by kappa- and mu-opioid receptors. In a previous paper, we reported that OFQ antagonizes inhibition of calcium channels mediated by kappa-opioid receptors. We report here that OFQ also antagonizes the inhibition of calcium channels mediated by mu-opioid receptor. Further, single-cell RT-PCR reveals that the antagonistic effect of OFQ is correlated with the presence of ORL1 mRNA in individual cells.