Staurosporine mobilizes Ca(2+) from secretory granules by inhibiting protein kinase C in rat submandibular acinar cells.
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.
Kim
Y J
YJ
Department of Oral Biology & Oral Science Research Center, BK21 Project for Medical Sciences, Yonsei University College of Dentistry, Shinchon-dong 134, Seodaemoon-gu, Seoul 120-752, Korea.
An
J M
JM
Shin
D M
DM
Lee
S-I
SI
Sugiya
H
H
Seo
J T
JT
D000818:Animals; D002118:Calcium / Q000819:agonists / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016257:Fura-2 / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology*; D013363:Submandibular Gland / Q000187:drug effects / Q000201:enzymology*
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium; D016257:Fura-2