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Nociceptin/orphanin FQ stimulates extracellular acidification and desensitization of the response involves protein

G Pei1, K Ling, L Pu

  • 1Shanghai Institute of Cell Biology, Chinese Academy of Sciences, People's Republic of China.

FEBS Letters
|July 21, 1997
PubMed

Insights

Nociceptin/orphanin FQ (N/OFQ) activates opioid receptor-like receptor 1 (ORL1) in CHO cells, causing desensitization mediated by protein kinase C. This signaling pathway is crucial for understanding ORL1 receptor function.

Area of Science:

  • Pharmacology
  • Cell Biology
  • Neuroscience

Background:

  • The opioid receptor-like receptor 1 (ORL1) is a G protein-coupled receptor involved in various physiological processes.
  • Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the ORL1 receptor.
  • Understanding ORL1-mediated signaling is crucial for developing targeted therapeutics.

Purpose of the Study:

  • To investigate the signaling events mediated by the ORL1 receptor in a Chinese hamster ovary (CHO) cell line.
  • To characterize the desensitization process of the ORL1 receptor upon stimulation with N/OFQ.
  • To elucidate the role of protein kinases in N/OFQ-induced ORL1 desensitization.

Main Methods:

  • Utilized a Chinese hamster ovary (CHO) cell line, CHO-ORL1, engineered to stably express the human ORL1 receptor.
  • Employed microphysiometry to measure extracellular acidification rate (ECAR) as an indicator of cellular metabolic activity.
  • Assessed the concentration-dependency and pertussis toxin-sensitivity of the N/OFQ-induced ECAR response.
  • Investigated ORL1 desensitization kinetics and the involvement of protein kinase C (PKC) and cAMP-dependent kinase (PKA) using specific inhibitors.

Main Results:

  • N/OFQ stimulation of CHO-ORL1 cells resulted in a concentration-dependent increase in ECAR.
  • The N/OFQ-induced ECAR response was sensitive to pertussis toxin, indicating G protein involvement.
  • Repeated N/OFQ exposure led to ORL1 desensitization, with recovery occurring with a half-life of approximately 12 minutes.
  • Inhibition of PKC significantly abolished N/OFQ-induced desensitization, while PKA inhibition had no effect.

Conclusions:

  • N/OFQ activates ORL1 receptors in CHO cells, leading to measurable changes in cellular metabolism via ECAR.
  • ORL1 desensitization is a rapid process that occurs upon prolonged or repeated N/OFQ stimulation.
  • Protein kinase C plays a critical role in the desensitization of the ORL1 receptor, while PKA is not involved.

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