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Cyclic AMP analogs induce synthesis, processing, and secretion of prepro nociceptin/orphanin FQ-derived peptides by

M J Sirianni1, K I Fujimoto, C S Nelson

  • 1Center for Research on Occupational and Environmental Toxicology, The Oregon Health Sciences University, Portland 97201, USA.

DNA and Cell Biology
|February 20, 1999
PubMed

Insights

Cyclic AMP (cAMP) analogs stimulate the secretion of orphanin (OFQ)-derived peptides from neuroblastoma cells. This secretion is regulated by opioids and stress response molecules, offering a valuable model for studying neuropeptide signaling.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Recent studies indicate cAMP analogs induce expression of prepro (pp) orphanin FA (OFQ)/nociceptin-related gene products in NS20Y mouse neuroblastoma cells.
  • Exposure to cAMP analogs promotes neurite outgrowth and dense-core vesicle formation in NS20Y cells.
  • Previous research identified an OFQ-like precursor (27K) in NS20Y cells, but no OFQ-related peptide secretion was detected.

Purpose of the Study:

  • To investigate whether NS20Y cells secrete ppOFQ-derived peptides when stimulated by the cAMP analog ctp-cAMP.
  • To characterize the regulation of OFQ peptide secretion by intracellular cAMP levels, opioids, and stress response mediators.

Main Methods:

  • Utilized reversed-phase high-performance liquid chromatography (RP-HPLC).
  • Employed a specific radioimmunoassay for OFQ(1-17).
  • Stimulated NS20Y cells with cAMP analogs and measured peptide secretion.

Main Results:

  • NS20Y cells secreted abundant OFQ-derived products upon stimulation with cAMP analogs.
  • Secretion was time- and concentration-dependent and reversible upon removal of cAMP analogs.
  • Opioid agonist D-Pen2-D-Pen5-enkephalin inhibited secretion, while dexamethasone abolished it.

Conclusions:

  • Intracellular cAMP levels modulate the biosynthesis, processing, and secretion of the OFQ neuropeptide transmitter system.
  • OFQ peptide secretion is regulated by opioids and molecules involved in the stress response.
  • The NS20Y cell system is a valuable model for studying OFQ-derived peptide regulation via signaling pathways.

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