Calcium signalling in bovine adrenal chromaffin cells: Additive effects of histamine and nicotine

In a previous report, we described the ability of two secretogogues, histamine and nicotine, to stimulate additive effects on catecholamine (CA) release and synapsin II phosphorylation in bovine adrenal chromaffin cells (BACC) [Firestone and Browning (1992), J. Neurochem., 58:441–447]. We hypothesized that these results were due to the combined effects on cytosolic Ca ++ of the two distinct signalling pathways. We therefore examined the intracellular Ca ++ signals stimulated by histamine and nicotine, alone and together. In Ca ++ ‐deficient medium, nicotine‐stimulated signals were abolished, whereas histamine‐stimulated signals were maintained, demonstrating that nicotine depended entirely on Ca ++ influx for its effects. Indeed, the nicotine‐stimulated signal could also be prevented using a Ca ++ channel blocker, nicardipine. Further, the observation that exposure of BACC to thapsigargin reduced histamine‐stimulated Ca ++ signals verified that histamine mobilizes Ca ++ from intracellular stores. Thus, the two secretogogues mobilize Ca ++ from distinct pools. When BACC were stimulated with the two secretogogues together, the resulting Ca ++ signal was greater than that from either alone. These data are consistent with a model in which two distinct sources of Ca ++ can summate within the cell, producing a greater Ca ++ signal and, hence, a greater effect on neurotransmitter release. © 1994 Wiley‐Liss, Inc.