CROSS-TALK BETWEEN CALCIUM AND CAMP-DEPENDENT INTRACELLULAR SIGNALING PATHWAYS - 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 either cAMP or cytosolic calcium can lead to synergistic responses. This study examined interactions, or crosstalk, between these two intracellular messengers and its implication for signaling in two secretory cell types, T-84 human colonic epithelial cells and rat pancreatic acinar 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 analogue of cAMP synergisticatly enhanced secretory responses to calcium-mobilizing hormones in both cell types, but paradoxically reduced overall calcium mobilization. The reduction in calcium mobilization could be attributed to an inhibition of calcium influx in T-84 cells, although a different mechanism likely operates in acinar cells, The effects of the cAMP analogue were reproduced by other agents that increase cAMP, Furthermore, econazole, an inhibitor of calcium influx, potentiated secretory responses to calcium-dependent stimulation in T-84 cells without 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-talk appears to regulate the extent of secretory responses.