We herein demonstrate the rapid effect of progesterone (PROG) on the intracellular Ca
2+ ([Ca
2+]
i) dynamics in GT1-7 cells. The cells were loaded with Calcium Green-1 AM and single-cell Ca
2+ imaging was performed by digital microscopic imaging. The frequency of spontaneous Ca
2+ oscillation was 0.09 Hz. A 20-min incubation with 1 μM PROG significantly suppressed the Ca
2+ oscillation down to 54% of the control frequency. The inhibitor of the classical PROG receptor, RU-486, completely blocked this PROG-induced suppression of Ca
2+ oscillation. The Ca
2+ oscillation was completely blocked by the treatment with nicardipine, an inhibitor of the voltage-sensitive Ca
2+ channel, but not blocked by the treatment with thapsigargin, an inhibitor of the Ca
2+ pump of microsomes. Therefore, the PROG-induced suppression of the Ca
2+ oscillation may be due to modulation of the voltage-dependent Ca
2+ channel. These results imply that PROG rapidly (within 20 min) drives Ca
2+ signaling via the nongenomic pathway dependent on classical PROG receptors. The existence of the PROG receptor was confirmed by a Western blot analysis.
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