Effect And Mechanism Of Sigma-1 Receptor Agonist Pre-084 On The Intrasynaptosomal Ca²⁺ Concentration

A number of evidence showed that sigma-1 receptor could regulate intracellular Ca2+ concentration. However, few studies examined the effect of activation of sigma-1 receptor on intracellular Ca2+ concentration at presynaptic sites. The present study examined the effect of sigma-1 receptor agonists on intracellular Ca2+ concentration at presynaptic sites using synaptosomes from the medial prefrontal cortex, hippocampus and the striatum. Moreover, we further studied the mechanism of the effect of sigma-1 receptor agonist on intrasynaptosomal Ca2+ concentration in rat medial prefrontal cortex. The results showed that sigma-1 receptor agonists increase intrasynaptosomal Ca2+ concentration in the medial prefrontal cortex, but not in the hippocampus and striatum; Extracellular Ca2+ chelator EGTA cancels the effect of sigma-1 receptor agonist, but intracellular Ca2+ store depleter thapsigargin does not; L-type Ca2+ channel blockers cancel the effect of sigma-1 receptor agonist, but NMDA channel blocker does not; PKC inhibitor cancels the effect of sigma-1 receptor agonist, but PKA inhibitor does not; PKCβI inhibitor cancels the effect of sigma-1 receptor agonist, but PKCβⅡinhibitor does not. These results suggest that Activation of sigma-1 receptor increases intrasynaptosomal Ca2+ concentration via PKC/L-type calcium channel signaling pathway in rat medial prefrontal cortex.