In vitro and in vivo pharmacological characterization of the nociceptin/orphanin FQ receptor ligand Ac-RYYRIK-ol.

摘要: Abstract It was recently reported that the hexapeptide Ac-RYYRIK-ol binds with high affinity nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptors and competitively antagonizes N/OFQ actions in mouse vas deferens assay. Here we further describe vitro vivo pharmacological features of this NOP receptor ligand. In brain homogenate degradation half life (2.48 min) significantly higher than parent compound Ac-RYYRIK-NH 2 (1.20 min). electrically stimulated deferens, (10–1000 nM) antagonized inhibitory effect (pA  = 8.46), while isolated colon mimicked contractile effects thus behaving as a agonist (pEC 50  = 9.09). This latter no longer evident tissues taken from mice knock out for gene (NOP −/− ). mice, similarly to N/OFQ, (dose range 0.001–1 nmol) produced: i) pronociceptive after intracerebroventricular (i.c.v.) administration antinociceptive when given intrathecally (i.t.) tail withdrawal assay; ii) inhibition locomotor activity iii) stimulation food intake supraspinal administration. Finally, forced swimming test, inactive per se, but reversed antidepressant-like elicited by selective antagonist UFP-101 ([Nphe 1 ,Arg 14 ,Lys 15 ]N/OFQ-NH Thus, all these assays showing however potency. conclusion, displayed complex profile which is likely due low efficacy nature novel ligand receptor. The potency, selectivity action, effectiveness make useful tool future studies field its