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Morphine but not fentanyl and methadone affects mitochondrial membrane potential by inducing nitric oxide release in

D Mastronicola1, E Arcuri, M Arese

  • 1Department of Biochemistry A. Rossi-Fanelli, Università di Roma La Sapienza, Piazzale Aldo Moro 5, 00185 Rome, Italy.

Cellular and Molecular Life Sciences : CMLS
|December 8, 2004
PubMed

Insights

Morphine affects human glioma cells by reducing mitochondrial membrane potential via nitric oxide (NO) release. This finding reveals new opioid pathways relevant to therapy and toxicology.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Opioids, such as morphine, are widely used for pain management.
  • The precise cellular mechanisms underlying opioid effects, particularly in non-neuronal cells like gliomas, require further elucidation.
  • Mitochondrial function is critical for cellular health and can be influenced by various signaling pathways.

Purpose of the Study:

  • To investigate the effect of morphine on mitochondrial membrane potential in human glioma cells.
  • To identify the specific receptors and intracellular pathways involved in morphine's action on glioma mitochondria.
  • To explore the role of nitric oxide (NO) in mediating these effects.

Main Methods:

  • Treatment of human glioma cells with varying concentrations of morphine.
  • Assessment of mitochondrial membrane potential using established assays.
  • Investigation of receptor involvement using naloxone, and pathway analysis with desipramine and L-NAME (nitric oxide synthase inhibitor).
  • Comparative analysis with other opioids like fentanyl and methadone.

Main Results:

  • Morphine, at nanomolar concentrations, significantly altered mitochondrial membrane potential in human glioma cells.
  • This effect was specific to morphine, naloxone-sensitive, and potentiated by desipramine.
  • Fentanyl and methadone did not induce similar mitochondrial impairment.
  • The effect was blocked by L-NAME, indicating the involvement of nitric oxide (NO) synthase.

Conclusions:

  • Morphine induces nitric oxide (NO) release in cultured glioma cells, which subsequently decreases mitochondrial membrane potential.
  • This NO-mediated pathway represents a novel intracellular mechanism of action for morphine.
  • The findings offer new insights into the therapeutic and toxicological aspects of opioids, particularly concerning glioma cells.

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