Fentanyl inhibits the uptake of [3H]noradrenaline in cultured neuronal cells.
We have examined how fentanyl modulates [3H]noradrenaline uptake in two cultured neuronal cell preparations, the human neuroblastoma SH-SY5Y and the rat phaeochromocytoma PC12. Fentanyl produced a significant, dose-dependent inhibition of [3H]noradrenaline uptake at concentrations in excess of 0.1 mumol litre-1 (P < 0.05) and 0.3 mumol litre-1 (P < 0.05) for PC12 and SH-SY5Y cells, respectively. However, these values exceed the serum concentration of fentanyl required to produce analgesia. At the maximum concentration examined (100 mumol litre-1), fentanyl produced 85-95% inhibition of uptake. This effect was not antagonized by naloxone, implying a nonopioid mechanism of action. Imipramine 1 mumol litre-1 reduced [3H]noradrenaline uptake by 65-70% but morphine, in contrast to fentanyl, had no effect (P > 0.1).
Atcheson
R
R
University Department of Anaesthesia, Leicester Royal Infirmary.
Rowbotham
D J
DJ
Lambert
D G
DG
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology*; D006801:Humans; D007099:Imipramine / Q000493:pharmacokinetics; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000493:pharmacokinetics*; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured
D009270:Naloxone; D009020:Morphine; D007099:Imipramine; D005283:Fentanyl; D009638:Norepinephrine