Fluoride causes suppression of neurite outgrowth in human neuroblastoma via an influx of extracellular calcium.

We have used human neuroblastoma NB-OK1 cells to investigate the regulatory mechanism of neurite outgrowth. Sodium fluoride suppressed forskolin-stimulated neurite outgrowth in a dose-dependent manner. Sodium fluoride increased intracellular free calcium concentrations ([Ca2+]i), but had no effect on the cAMP level, arachidonic acid (AA) release or phosphoinositide (PI) hydrolysis in NB-OK1 cells. The calcium response of sodium fluoride was dependent on the extracellular Ca2+. The dose-response curve for stimulation of [Ca2+]i elicited by sodium fluoride was similar to that for suppression of neurite outgrowth. The suppressive effect of sodium fluoride on neurite outgrowth was inhibited by nonspecific Ca2+ entry blocker Mn2+ but not by L-, N- and T-type Ca2+ channel blockers. Hence we describe for the first time a possible role for calcium signaling in the regulation of neurite outgrowth by a G protein activator in the human neuron-derived cell line.