CROSS-TALK BETWEEN CALCIUM AND CAMP-DEPENDENT INTRACELLULAR SIGNALINGPATHWAYS - IMPLICATIONS FOR SYNERGISTIC SECRETION IN T-84 COLONIC EPITHELIAL CELLS AND RAT PANCREATIC ACINAR-CELLS

Treatment of various cells with combinations of agents that increase e ither cAMP or cytosolic calcium can lead to synergistic responses. Thi s study examined interactions, or crosstalk, between these two intrace llular messengers and its implication for signaling in two secretory c ell types, T-84 human colonic epithelial cells and rat pancreatic acin ar cells. T-84 cell chloride secretion was measured in Ussing chambers , Acinar cell activation was monitored as amylase secretion, Cytosolic calcium was assessed via fura-2 microfluorimetry. A cell-permeant ana logue of cAMP synergisticatly enhanced secretory responses to calcium- mobilizing hormones in both cell types, but paradoxically reduced over all calcium mobilization. The reduction in calcium mobilization could be attributed to an inhibition of calcium influx in T-84 cells, althou gh a different mechanism likely operates in acinar cells, The effects of the cAMP analogue were reproduced by other agents that increase cAM P, Furthermore, econazole, an inhibitor of calcium influx, potentiated secretory responses to calcium-dependent stimulation in T-84 cells wi thout itself inducing secretion, We conclude that there is cross-talk between calcium and cAMP-dependent signaling pathways at the level of second messenger generation in two secretory cell types. This cross-ta lk appears to regulate the extent of secretory responses.