STAUROSPORINE ENHANCES CA2-CELLS( ENTRY INDUCED BY DEPLETION OF INTRACELLULAR CA2+ STORES IN RAT PAROTID ACINAR)

The effect of staurosporine on the Ca2+ signalling induced by the musc arinic receptor agonist carbachol (CCh) was studied in Fura-2-loaded r at parotid acinar cells. At concentrations > 1 nM, staurosporine dose- dependently enhanced the sustained increase in cytosolic free Ca2+ con centration ([Ca2+](i)), but did not affect the peak [Ca2+](i) seen lus t after stimulation. The enhancement of the sustained increase in [Ca2 +](i) was not attenuated by the protein kinase C activator, 4 beta-pho rbol 12-myristate 13-acetate, and not mimicked by another inhibitor of protein kinase C, K-252a, suggesting that the effect of staurosporine on the CCh-induced Ca2+ signalling may be due to a mechanism independ ent of the inhibitory action on protein kinase C. Staurosporine also e nhanced the increases in [Ca2+](i) induced by the microsomal Ca2+-ATPa se inhibitor thapsigargin (TG) and the Ca2+ ionophore ionomycin (lone) . When the cells were stimulated by CCh TG or lone in the absence of e xtracellular Ca2+, a transient increase in [Ca2+](i) due to Ca2+ relea se from intracellular stores was observed. This increase in [Ca2+](i) was unaffected by preincubation with staurosporine. However, when Ca2 was added to the extracellular medium after [Ca2+](i) had returned to the resting level, the increase in [Ca2+](i) was significantly enhanc ed by staurosporine. In addition, staurosporine accelerated the Mn2+ i nflux following the addition of CCh, TG, or lone. These results sugges t that staurosporine modulates the Ca2+ entry system activated by depl etion of intracellular Ca2+ stores in rat parotid acinar cells.