[Phe(1)Phi(CH2-NH)Gly(2)]nociceptin-(1-13)-NH2 acts as a partial agonist at ORL1 receptor endogenously expressed in mouse N1E-115 neuroblastoma cells

THE nociceptin derivative [Phe(1)Phi(CH2-NH)Gly(2)]-nociceptin-(1-13)-NH2 (Phe Phi noc) has been reported to act either as a simple antagonist or as a full agonist at the opioid receptor-like (ORL1) receptor. In the present study, we identified the expression of the ORL1 receptor in murine N1E-115 neuroblastoma cells and used this neuronal system to investigate the pharmacological activity of Phe Phi noc. Like nociceptin, Phe Phi noc stimulated the binding of [S-35]GTP gamma S (EC50 = 120 nM) and inhibited forskolin-stimulated [H-3]cAMP formation (EC50=3.3 nM). However, Phe Phi noc elicited maximal effects lower than those induced by nociceptin, and when combined with nociceptin potently antagonized the responses to the natural agonist (K-i = 0.9 nM). These data indicate that Phe Phi noc acts as a partial agonist at the ORL1 receptor endogenously expressed in N1E-115 cells. NeuroReport 10:1127-1131 (C) 1999 Lippincott Williams & Wilkins.