[Phe1phi(CH2-NH)Gly2]nociceptin-(1-13)-NH2 acts as a partial agonist at ORL1 receptor endogenously expressed in mouse N1E-115 neuroblastoma cells

Neuroreport. 1999 Apr 6;10(5):1127-31. doi: 10.1097/00001756-199904060-00041.

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.

MeSH terms

  • Animals
  • Colforsin / pharmacology
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / biosynthesis
  • Drug Combinations
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Mice
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Nociceptin
  • Nociceptin Receptor
  • Opioid Peptides / pharmacology*
  • Peptide Fragments / pharmacology*
  • Receptors, Opioid / agonists*
  • Receptors, Opioid / metabolism*
  • Tumor Cells, Cultured

Substances

  • Drug Combinations
  • Opioid Peptides
  • Peptide Fragments
  • Receptors, Opioid
  • nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-
  • Colforsin
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Cyclic AMP
  • Nociceptin Receptor
  • Oprl1 protein, mouse