FENTANYL INHIBITS THE UPTAKE OF [H-3] NORADRENALINE IN CULTURED NEURONAL CELLS

We have examined how fentanyl modulates [H-3]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 [H-3]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 non-opioid mechanism of action. Imipramine 1 mumol litre-1 reduced [H-3]noradrenaline uptake by 65-70% but morphine, in contrast to fentanyl, had no effect (P > 0.1).