Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 23, pp 2991–2997

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

Authors

  • D. Mastronicola
    • Department of Biochemistry ‘A. Rossi-Fanelli’Università di Roma ‘La Sapienza’
    • Centre of Advanced Molecular Diagnosis (DIMA), S. Andrea Hospital, The Faculty of Medicine IIUniversity of Rome ‘La Sapienza’
    • Pain Therapy and Palliative CareRegina Elena National Cancer Institute
  • E. Arcuri
    • Pain Therapy and Palliative CareRegina Elena National Cancer Institute
  • M. Arese
    • Department of Biochemistry ‘A. Rossi-Fanelli’Università di Roma ‘La Sapienza’
    • Centre of Advanced Molecular Diagnosis (DIMA), S. Andrea Hospital, The Faculty of Medicine IIUniversity of Rome ‘La Sapienza’
  • A. Bacchi
    • Department of Biochemistry ‘A. Rossi-Fanelli’Università di Roma ‘La Sapienza’
    • Centre of Advanced Molecular Diagnosis (DIMA), S. Andrea Hospital, The Faculty of Medicine IIUniversity of Rome ‘La Sapienza’
  • S. Mercadante
    • Division of Pain Therapy and Palliative CareCancer Institute La Maddalena
  • P. Cardelli
    • Department of OdontostomatologyThe University of Tor Vergata
  • G. Citro
    • Pain Therapy and Palliative CareRegina Elena National Cancer Institute
    • Department of Biochemistry ‘A. Rossi-Fanelli’Università di Roma ‘La Sapienza’
Research Article

DOI: 10.1007/s00018-004-4371-x

Cite this article as:
Mastronicola, D., Arcuri, E., Arese, M. et al. CMLS, Cell. Mol. Life Sci. (2004) 61: 2991. doi:10.1007/s00018-004-4371-x

Abstract.

We have observed that treatment of human glioma cells with morphine in the nanomolar range of concentration affects the mitochondrial membrane potential. The effect is specific to morphine and is mediated by naloxone-sensitive receptors, and is thus better observed on glioma cells treated with desipramine; moreover, the mitochondrial impairment is not inducible by fentanyl or methadone treatment and is prevented by the nitric oxide (NO) synthase inhibitor L-NAME. We conclude that in cultured glioma cells, the morphine-induced NO release decreases the mitochondrial membrane potential, as one might expect based on the rapid inhibition of the respiratory chain by NO. The identification of new intra-cellular pathways involved in the mechanism of action of morphine opens additional hypotheses, providing a novel rationale relevant to the therapy and toxicology of opioids.

Key words.

Cytochrome oxidasenitrosative stressopioid responsivenessbioenergeticsantinociceptive drugradicals

Copyright information

© Birkhäuser Verlag, Basel 2004