[Phe1phi(CH2-NH)Gly2]nociceptin-(1-13)-NH2 Acts As A ... - PubMed

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Abstract

The nociceptin derivative [Phe1phi(CH2-NH)Gly2]-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 [35S]GTPgammaS (EC50 = 120 nM) and inhibited forskolin-stimulated [3H]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 (Ki = 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.

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  • Identification of the G-protein-coupled ORL1 receptor in the mouse spinal cord by [35S]-GTPgammaS binding and immunohistochemistry. Narita M, Mizoguchi H, Oji DE, Dun NJ, Hwang BH, Nagase H, Tseng LF. Narita M, et al. Br J Pharmacol. 1999 Nov;128(6):1300-6. doi: 10.1038/sj.bjp.0702907. Br J Pharmacol. 1999. PMID: 10578145 Free PMC article.
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  • Partial agonist behaviour depends upon the level of nociceptin/orphanin FQ receptor expression: studies using the ecdysone-inducible mammalian expression system. McDonald J, Barnes TA, Okawa H, Williams J, Calo' G, Rowbotham DJ, Lambert DG. McDonald J, et al. Br J Pharmacol. 2003 Sep;140(1):61-70. doi: 10.1038/sj.bjp.0705401. Epub 2003 Aug 11. Br J Pharmacol. 2003. PMID: 12967935 Free PMC article.
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  • Pharmacology of nociceptin and its receptor: a novel therapeutic target. Calo' G, Guerrini R, Rizzi A, Salvadori S, Regoli D. Calo' G, et al. Br J Pharmacol. 2000 Apr;129(7):1261-83. doi: 10.1038/sj.bjp.0703219. Br J Pharmacol. 2000. PMID: 10742280 Free PMC article. Review.

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