Neuropeptide Nociceptin Orphanin FQ

G protein-coupled opioid receptor-like 1 (ORL1) receptor is found in both central and peripheral nervous systems (Meunier, 1997). Its agonist neuropeptide noci-ceptin/orphanin FQ (N/OFQ) is located in the central nervous system and is a critical element in biological responses such as pain and anxiety (Meunier, 1997). There is much controversy surrounding the biological action of N/OFQ as peptide inhibitors have shown to result in potentiating nociception centrally but ameliorating it peripherally (Tian and Han, 2000). Specific inhibitors of this peptide would prove useful in elucidating it as the mechanism of nociception and control of such pain. Using an RNA library, 13 rounds of selection were performed on immobilized N/OFQ and after truncation analysis, two spiegelmers, a 61-mer called NOX 2149 and a 65-mer called NOX 2137a/b, were identified, having dissociation constants of 300nmol/L and 600nmol/L respectively (Faulhammer et al., 2004). Both aptamers were tested for their ability to inhibit N/OFQ from binding to its receptor, resulting in IC50 of 110nmol/L for NOX 2149 and 300nmol/L for NOX 2137a/b. The aptamers were also evaluated in a functional GTPgS, where the aptamers were measured for their ability to block N/OFQ-mediated [35S]GTPgS into membranes containing human ORL1 receptor. Both aptamers prevented such incorporation, with NOX 2149 having the most significant inhibition.

Finally, in ORL1-GIRK1-cRNA oocytes, addition of N/OFQ produced an inward current of-318nA that was ameliorated by 50% when NOX 2149 was concurrently added (P< 0.0001) (Faulhammer et al., 2004).

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