Fentanyl increases intracellular Ca2+ concentrations in SH-SY5Y cells.
Classically, opioids inhibit Ca2+ influx, but recent reports suggest opioids may also stimulate Ca2+ entry. Therefore, we have measured the effect of opioids on intracellular Ca2+ ([Ca2+]i), fluorimetrically, in Fura-2-loaded SH-SY5Y cells. Fentanyl 0.3 mumol litre-1 caused a mean increase in [Ca2+]i of 18.8 (SEM 2.1) nmol litre-1 in some (30.3%) batches of SH-SY5Y cells. In responding cells, the fentanyl-induced increase in [Ca2+]i was dose-dependent, with an EC50 of 0.73 mumol litre-1. This response was naloxone-reversible, and the delta opioid agonist [D-Pen2,5]enkephalin had no effect on [Ca2+]i, suggesting the fentanyl-induced Ca2+ response was entirely mediated by the mu opioid receptor. Fentanyl 0.3 mumol litre-1 increased [Ca2+]i without preactivation of phospholipase C by another agonist, and this was markedly reduced by Ni2+ 2.5 mmol litre-1. These data suggest that mu opioids directly increase [Ca2+]i by stimulating Ca2+ influx in SH-SY5Y cells.
Wandless
A L
AL
University Department of Anaesthesia, Leicester Royal Infirmary.
Smart
D
D
Lambert
D G
DG
D000701:Analgesics, Opioid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D014407:Tumor Cells, Cultured
D000701:Analgesics, Opioid; D015220:Calcium Channels; D002118:Calcium; D005283:Fentanyl