Staurosporine mobilizes Ca²⁺ from secretory granules by inhibiting protein kinase C in rat submandibular acinar cells

Staurosporine was previously shown to mobilize Ca²⁺ from the thapsigargin-insensitive Ca²⁺ store in rat submandibular acinar cells. However, the nature of the store is not yet known. Therefore, in the present study, the staurosporine-releasable intracellular Ca²⁺ store was characterized. Staurosporine increased the cytosolic Ca²⁺ concentration ([Ca²⁺]_c) after the inositol 1,4,5-trisphosphate (IP₃)-sensitive Ca²⁺ store was depleted. Ionomycin caused only small increases in [Ca²⁺]_c after the depletion of the IP₃-sensitive Ca²⁺ store, whereas ionomycin+monensin caused large increases. However, ionomycin+monensin did not increase [Ca²⁺]_c when added after [Ca²⁺]_c was increased by staurosporine, indicating that the acidic Ca²⁺ store was the main source of Ca²⁺. The acidic Ca²⁺ store appeared to be associated with secretory granules, since ionomycin+monensin-and staurosporine-induced [Ca²⁺]_c increases were significantly reduced when the acinar cells were degranulated. The effect of staurosporine on [Ca²⁺]_c was mimicked by other protein kinase C inhibitors. Therefore, we conclude that staurosporine mobilizes Ca²⁺ from secretory granules, probably through the inhibition of protein kinase C in rat submandibular acinar cells.