Fentanyl inhibits the release of [3H]noradrenaline from SH-SY5Y human neuroblastoma cells.
We have examined the effect of fentanyl on [3H]noradrenaline release in a human neuroblastoma cell preparation, SH-SY5Y. Fentanyl produced a significant, concentration-dependent inhibition of [3H]noradrenaline 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, respectively. The small difference in IC50 between the two evoking stimuli may be explained by the weak binding affinity of fentanyl to muscarinic receptors (Ki = 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-evoked release, respectively; these values are considerably in excess of the serum concentration of fentanyl required to produce analgesia. Naloxone failed to antagonize the fentanyl inhibition and, furthermore, morphine and an enkephalin had no effect on evoked release, implying a non-opioid receptor mediated effect.
Atcheson
R
R
University Department of Anaesthesia, Leicester Royal Infirmary.
Rowbotham
D J
DJ
Lambert
D G
DG
D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000378:metabolism; D002454:Cell Differentiation; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005283:Fentanyl / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009020:Morphine / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000037:antagonists & inhibitors; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004745:Enkephalins; D011976:Receptors, Muscarinic; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D001285:Atropine; D002217:Carbachol; D011188:Potassium; D005283:Fentanyl; D009638:Norepinephrine