Staurosporine Mobilizes Ca2+ from Secretory Granules by Inhibiting Protein Kinase C in Rat Submandibular Acinar Cells

Abstract

Staurosporine was previously shown to mobilize Ca(2+) from the thapsigargin-insensitive Ca(2+) 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 Ca(2+) store was characterized. Staurosporine increased the cytosolic Ca(2+) concentration ([Ca(2+)](c)) after the inositol 1,4,5-trisphosphate (IP(3))-sensitive Ca(2+) store was depleted. Ionomycin caused only small increases in [Ca(2+)](c) after the depletion of the IP(3)-sensitive Ca(2+) store, whereas ionomycin+monensin caused large increases. However, ionomycin+monensin did not increase [Ca(2+)](c) when added after [Ca(2+)](c) was increased by staurosporine, indicating that the acidic Ca(2+) store was the main source of Ca(2+). The acidic Ca(2+) store appeared to be associated with secretory granules, since ionomycin+monensin- and staurosporine-induced [Ca(2+)](c) increases were significantly reduced when the acinar cells were degranulated. The effect of staurosporine on [Ca(2+)](c) was mimicked by other protein kinase C inhibitors. Therefore, we conclude that staurosporine mobilizes Ca(2+) from secretory granules, probably through the inhibition of protein kinase C in rat submandibular acinar cells.

Contributions of Intracellular Compartments to Calcium Dynamics: Implicating an Acidic Store

“…All of these results point toward IGs as a GPN‐sensitive functional Ca 2+ store in β‐cells. Dense‐core secretory granules have been proposed as functional Ca 2+ stores in, for example, the PC‐12 cell line (38) and primary rat submandibular salivary glands (39), though these claims are less substantiated than ours are here. An NAADP‐ and GPN‐sensitive pool has been implicated in responses of MIN‐6 cells to glucose (19).…”

Stimulation of epidermal calcium gradient loss and increase in TNF‐α and IL‐1α expressions by glycolic acid in murine epidermis

“…The intracellular Ca 2+ concentration ([Ca 2+ ] i ) was measured in the primary cultured mice keratinocytes, following a previously described method with a slight modification (23). Briefly, the cultured cells were loaded with 4 M Fura‐2 AM for 30 min in a HEPES‐buffered solution containing 130 mM NaCl, 3 mM KCl, 2 mM MgCl 2 , 0.03 mM CaCl 2 , 25 mM HEPES and 10 mM D‐glucose (pH 7.4).…”