Pertussis toxin-insensitive signaling of the ORL1 receptor: coupling to Gz and G16 proteins

J Neurochem. 1998 Nov;71(5):2203-10. doi: 10.1046/j.1471-4159.1998.71052203.x.

Abstract

Nociceptin/OFQ is the endogenous ligand for the G protein-coupled opioid receptor-like (ORL1) receptor. To elucidate the cellular functions of the ORL1 receptor, we examined its ability to interact with Gz and G16, two pertussis toxin (PTX)-insensitive G proteins that are known molecular partners for the opioid receptors. In HEK 293 cells transiently expressing the ORL1 and dopamine D1 receptors, nociceptin/OFQ dose-dependently inhibited dopamine-stimulated cyclic AMP (cAMP) accumulation in a PTX-sensitive manner. However, PTX failed to block the nociceptin/OFQ-induced inhibition of dopamine-stimulated cAMP accumulation in HEK 293 cells co-expressing the alpha-subunit of Gz. This result indicates functional interaction between the ORL1 receptor and Gz. A similar result was obtained with retinoic acid-differentiated SH-SY5Y cells, which endogenously express both the ORL1 receptor and Gz. When the ORL1 receptor was transiently co-expressed in COS-7 cells with the alpha-subunit of G16, nociceptin/OFQ dose-dependently stimulated the formation of inositol phosphates. Nociceptin-induced stimulation of phospholipase C was absolutely dependent on the co-expression of alpha16 and exhibited the appropriate ligand selectivity. In terms of its ability to interact with PTX-insensitive G proteins, the ORL1 receptor behaves very much like the opioid receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Cell Line
  • Drug Resistance
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Opioid Peptides / pharmacology
  • Pertussis Toxin*
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid / physiology
  • Signal Transduction / drug effects*
  • Type C Phospholipases / metabolism
  • Virulence Factors, Bordetella / pharmacology*

Substances

  • Adenylyl Cyclase Inhibitors
  • Opioid Peptides
  • Receptors, Opioid
  • Virulence Factors, Bordetella
  • nociceptin
  • nociceptin receptor
  • Pertussis Toxin
  • Type C Phospholipases
  • GTP-Binding Proteins