MULTIPLE EFFECTS OF OPIATES ON INTRACELLULAR CALCIUM LEVEL AND ON CALCIUM-UPTAKE IN 3 NEURONAL CELL-LINES

The present study examines the modulation by opiates of intracellular calcium levels and calcium entry, using fura-2 imaging and Ca-45(2+) u ptake, in three neuronal cell lines. We show that opiates (10(-7)-10(- 5) M morphine and 10(-9)-10(-7) M etorphine) exert both inhibitory and excitatory effects on KCl-induced elevation in intracellular calcium level in SK-N-SH, NG108-15 and NMB cell lines. In addition, opiates el evate basal (non KCl-stimulated) intracellular calcium level in all th ree cell cultures. Ca-45(2+) uptake is augmented by opiates in SK-N-SH cells and this stimulatory effect is not blocked by pertussis toxin. In NMB cells, an additional inhibitory effect of opiates on basal calc ium takes place: opiates reduce intracellular calcium level as measure d by fura-2, and decrease calcium influx as detected by Ca-45(2+) upta ke. The heterogeneity in the opioid regulation of calcium could not be attributed to the type of opioid drug, neither to its concentration n or to the experimental conditions, since neighboring cells within the same culture responded differently.