The nociceptin/orphanin FQ receptor ligand acetyl-RYYRIK-amide exhibits antagonistic and agonistic properties

摘要: Abstract The hexapeptide acetyl-RYYRIK-amide (Ac-RYYRIK-NH2) has recently been reported to act as partial agonist of the nociceptin/orphanin FQ (noc/OFQ) receptor expressed in CHO cells. In addition, this peptide acts a competitive antagonist noc/OFQ-stimulated GTPγ35S binding rat brain membranes well noc/OFQ-evoked chronotropic effect cardiomyocytes. contrast antagonism, present study, Ac-RYYRIK-NH2 was found behave an at noc/OFQ receptors, affecting spontaneous locomotor activity. When administered intracerebroventricularly (i.c.v.), and inhibited activity mice with ID50 1.1 0.07 nmol, respectively. Co-administration both peptides lead additive effects. higher potency could not be clearly explained by differential metabolism, because vivo microdialysis striatum vitro metabolic inactivation mouse revealed extensive peptides. Similar Ac-RYYRIK-NH2, [Phe1psi(CH2-NH)Gly2]noc/OFQ(1–13)-NH2 ([F/G]NC(1–13)NH2) (Schild constant 3.83 nM) sections, although several reports have shown that exhibits CNS. Changes optimum conditions assay for GTP increased low agonism response. To explain discrepancy between antagonism G protein coupling [F/G]NC(1–13)NH2, it is suggested receptor/G native systems may sufficient evoke full biologic responses. extent reserve vary different systems, thus explaining why [F/G]NC(1–13)NH2 were exhibit antagonist, agonist, or even properties, depending on system studied.