Characterization of nociceptin binding sites by novel peptide analogs and radioprobes

A number of new synthetic nociceptin ligands were studied in receptor binding and functional tests in rat brain membranes and in cloned systems. Ligand binding experiments were performed with three different radioprobes developed in our lab. The nociceptin derivatives exhibited high affinity in competition experiments. Receptor‐mediated G‐protein activation was determined in ³⁵S]GTPgS binding assays. Among the new structures examined, Ac‐RYYRIK‐ol was found to be only a weak stimulator by itself, whereas this compound inhibited receptor‐mediated G‐protein activation. These data suggest that Ac‐RYYRIK‐ol is a high affinity peptide antagonist for the nociceptin receptor. Acknowledgements: Supported by the Hungarian Scientific Research Fund OTKA T‐035211, T‐033078, T‐030841, and the Ministry of Education, NKFP 1/027 Hungary.