The σ receptor agonist (+)-pentazocine increases store-operated Ca entry in MCF7σ and SK-N-SH cell lines.

Background: The intracellular [Ca] is modulated by σ receptors. An important component of the cellular machinery governing the intracellular [Ca] is Store-Operated Calcium Entry (SOCE). Here we want to investigate whether ligands of σ receptors affect SOCE.

Methods: The intracellular [Ca] was monitored, with the fluorescent Ca-sensitive probe Fura-2, in four cell lines with a different expression of σ receptors, namely MCF7 (expressing σ receptors with a low density and overexpressing σ receptors), MCF7σ (overexpressing σ receptors), SK-N-SH, and HT-29.

Results: When thapsigargin was used to deplete intracellular Ca stores, in a Ca-free incubation medium, the Ca influx (following Ca re-addition) was significantly increased by 1μM (+)-pentazocine (σ receptor agonist) in MCF7σ (by 22.5%) and SK-N-SH (by 45.6%), but not in HT-29 and MCF7 cells. We have used, as a second approach, the "Mn quenching" protocol. In MCF7σ cells, after thapsigargin treatment, the fluorescence quenching induced by Mn influx (evidence of Ca influx) was significantly increased (by 25.8%) by 1μM (+)-pentazocine, significantly decreased (by 18.0%) by BD1063 (σ receptor antagonist), and not affected by the presence of both ligands. These effects were not observed in MCF7 cells. Finally, in MCF7 cells, 1μM PB28 (σ receptor agonist), did not affect both the Ca response after Ca re-addition and the fluorescence quenching induced by Mn influx.

Conclusions: We propose that the σ receptor agonist (+)-pentazocine increases SOCE in MCF7σ and SK-N-SH cell lines. The σ receptor agonist PB28 does not affect SOCE in MCF7 cells.