Research Article Open Access

Naloxone benzoylhydrazone activates Extracellular Signal-Regulated Protein Kinases and modulates Nociceptin Opioid Peptide Receptor activity

Deepak R. Thakker1, Ghazi F. Altememi1, Chitra D. Mandyam2, Hala Ibrahim1, Vanessa I. Ramirez3 and Kelly M. Standifer3
  • 1 University of Houston, United States
  • 2 The Scripps Research Institute, United States
  • 3 University of Oklahoma Health Sciences Center, United States

Abstract

Naloxone benzoylhydrazone (NalBzoH) is often used as a nociceptin opioid peptide (NOP) receptor antagonist. However, NalBzoH is also a mixed μ antagonist/κ and δ opioid agonist and its actions at the NOP receptor range from an antagonist to partial agonist, depending on the effector response/system studied. We now report that NalBzoH activates endogenously expressed κ3 opioid, but not NOP, receptors to stimulate extracellular signal-regulated protein kinases 1/2 and, subsequently, to mediate changes in the expression of tyrosine hydroxylase and G protein-coupled receptor kinase 2 in SH-SY5Y human neuroblastoma cells. Furthermore, pretreatment with NalBzoH produces homologous desensitization of the κ3 opioid receptor as well as heterologous desensitization of the NOP receptor. In contrast, pretreatment with the NOP agonist, orphanin FQ/nociceptin (OFQ/N), desensitizes only NOP but not the NalBzoH response, suggesting the involvement of a receptor, distinct from NOP, in mediating the actions of NalBzoH in SH-SY5Y cells.

American Journal of Pharmacology and Toxicology
Volume 2 No. 2, 2007, 51-59

DOI: https://doi.org/10.3844/ajptsp.2007.51.59

Submitted On: 31 January 2007 Published On: 30 June 2007

How to Cite: Thakker, D. R., Altememi, G. F., Mandyam, C. D., Ibrahim, H., Ramirez, V. I. & Standifer, K. M. (2007). Naloxone benzoylhydrazone activates Extracellular Signal-Regulated Protein Kinases and modulates Nociceptin Opioid Peptide Receptor activity. American Journal of Pharmacology and Toxicology, 2(2), 51-59. https://doi.org/10.3844/ajptsp.2007.51.59

  • 3,280 Views
  • 2,645 Downloads
  • 2 Citations

Download

Keywords

  • orphanin FQ/nociceptin
  • tyrosine hydroxylase
  • G protein-coupled receptor kinase 2