FENTANYL INHIBITS THE RELEASE OF [H-3] NORADRENALINE FROM SH-SY5Y HUMAN NEUROBLASTOMA-CELLS

We have examined the effect of fentanyl on [H-3]noradrenaline release in a human neuroblastoma cell preparation, SH-SY5Y. Fentanyl produced a significant, concentration-dependent inhibition of [H-3]noradrenalin e release with IC50 values of 5.5 x 10(-6) mol litre(-1) and 15.5 x 10 (-6) mol litre(-1) for carbachol- and potassium-evoked release, respec tively. The small difference in IC50, between the two evoking stimuli may be explained by the weak binding affinity of fentanyl to muscarini c receptors (K-i = 570 nmol litre(-1)). The minimum concentrations at which a significant effect was observed were 0.3 x 0.10(-6) mol litre( -1) and 10.0 x 10(-6) mol litre(-1) for carbachol- and potassium-evoke d release, respectively, these values are considerably in excess of th e serum concentration of fentanyl required 50 produce analgesia. Nalox one failed to antagonize the fentanyl inhibition and, furthermore, mor phine and an enkephalin had no effect on evoked release, implying a no n-opioid receptor mediated effect.