Neurite Outgrowth Stimulated by Oxytocin Is Modulated by Inhibition of the Calcium Voltage-Gated Channels.

ABSTRACT

Neuropeptide oxytocin contributes to the regulation of the neuron differentiation and cell morphology. However, the precise mechanisms are not yet fully understood. Oxytocin receptor function and its coupling to calcium entry are obvious objects of interest in relation to the neuron morphology. Postsynaptic scaffolding proteins including SHANK proteins interact with other synaptic molecules and change dendritic morphology. SH-SY5Y neuroblastoma cell line represents a useful neurobiological in vitro model to study the short-term oxytocin effects on neurite outgrowth and underlying mechanisms. In the present study, we show that oxytocin induces an increase in the intracellular calcium in SH-SY5Y cells. Specificity of the calcium influx was verified by blockade of the oxytocin receptors with oxytocin receptor antagonist L-371,257. Neurite outgrowth stimulated by oxytocin was inhibited by specific voltage-gated calcium channel blockers. The exposure of SH-SY5Y cells to oxytocin resulted in a significant increase in the gene expression of SHANK1 and SHANK3 proteins. Overall, the present data indicate that oxytocin may contribute to the regulation of scaffolding proteins expression known to be associated with clusters of calcium channels at the cell membrane. It appears that oxytocin stimulated neurite outgrowth is, at least, in part dependent on the voltage-gated calcium channels.