Morphine but not fentanyl and methadone affects mitochondrial membrane potential by inducing nitric oxide release in glioma cells.
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.
Mastronicola
D
D
Department of Biochemistry A. Rossi-Fanelli, Università di Roma La Sapienza, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Arcuri
E
E
Arese
M
M
Bacchi
A
A
Mercadante
S
S
Cardelli
P
P
Citro
G
G
Sarti
P
P
D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D045744:Cell Line, Tumor; D003576:Electron Transport Complex IV / Q000378:metabolism; D005283:Fentanyl / Q000494:pharmacology*; D005609:Free Radicals; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects*; D008691:Methadone / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D015398:Signal Transduction; D013053:Spectrophotometry; D013997:Time Factors
D000759:Adjuvants, Anesthesia; D000701:Analgesics, Opioid; D005609:Free Radicals; D009294:Narcotics; D009573:Nitrites; D009569:Nitric Oxide; D009020:Morphine; D003576:Electron Transport Complex IV; D008691:Methadone; D005283:Fentanyl; D019331:NG-Nitroarginine Methyl Ester