The σ1 receptor agonist (+)-pentazocine increases store-operated Ca(2+) entry in MCF7σ1 and SK-N-SH cell lines.

BACKGROUND: The intracellular [Ca(2+)] is modulated by σ receptors. An important component of the cellular machinery governing the intracellular [Ca(2+)] is Store-Operated Calcium Entry (SOCE). Here we want to investigate whether ligands of σ receptors affect SOCE.

METHODS: The intracellular [Ca(2+)] was monitored, with the fluorescent Ca(2+)-sensitive probe Fura-2, in four cell lines with a different expression of σ receptors, namely MCF7 (expressing σ1 receptors with a low density and overexpressing σ2 receptors), MCF7σ1 (overexpressing σ1 receptors), SK-N-SH, and HT-29.

RESULTS: When thapsigargin was used to deplete intracellular Ca(2+) stores, in a Ca(2+)-free incubation medium, the Ca(2+) influx (following Ca(2+) re-addition) was significantly increased by 1μM (+)-pentazocine (σ1 receptor agonist) in MCF7σ1 (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(2+) quenching" protocol. In MCF7σ1 cells, after thapsigargin treatment, the fluorescence quenching induced by Mn(2+) influx (evidence of Ca(2+) influx) was significantly increased (by 25.8%) by 1μM (+)-pentazocine, significantly decreased (by 18.0%) by BD1063 (σ1 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 (σ2 receptor agonist), did not affect both the Ca(2+) response after Ca(2+) re-addition and the fluorescence quenching induced by Mn(2+) influx.

CONCLUSIONS: We propose that the σ1 receptor agonist (+)-pentazocine increases SOCE in MCF7σ1 and SK-N-SH cell lines. The σ2 receptor agonist PB28 does not affect SOCE in MCF7 cells.