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.
Firestone
J A
JA
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Browning
M D
MD
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D009529:Nicardipine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D013729:Terpenes; D004533:Egtazic Acid; D019284:Thapsigargin; D009538:Nicotine; D006632:Histamine; D009529:Nicardipine; D000252:Calcium-Transporting ATPases; D002118:Calcium