Effects of nitroprusside and nicorandil on catecholamine secretion and calcium mobilization in cultured bovine adrenal chromaffin cells.

The effects of nitroprusside and nicorandil on catecholamine secretion and free intracellular Ca 2+ ([Ca 2+ ]i) mobilization in bovine adrenal chromaffin cells were studied to evaluate the role of the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in the regulation of a (Ca 2+ ];-dependent secretory process. These effects were compared with those of nifedipine, a typical voltage-dependent Ca 2+ channel blocker. Carbachol produced a rapid increase followed by a sustained increase of (Ca 2+ ]; (Ca 2+ transient) in cultured bovine adrenal chromaffin cells. Both nitroprusside and nicorandil accelerated the decrease in [Ca 2+ ] , without changing the peak values of the initial (Ca 2+ ]; increase of Ca 2+ transient. These drugs, however, did not affect carbachol-induced catecholamine secretion, suggesting that secretion is related to the initial [Ca 2+ ]; increase and not to a late sustained (Ca 2+ ]; increases. However, nifedipine reduced the peak and duration of carbachol-induced (Ca 2+ ]; increases and decreased the secretion of catecholamines. Diethylamine/NO complex, an NO donor, and dibutyryl-cGMP produced similar changes in Ca 2+ transient and did not alter catecholamine secretion, suggesting that the effects of nitroprusside and nicorandil were mediated by the NO/cGMP pathway. These results indicated that the pattern of Ca 2+ transient, especially the initial increase in (Ca 2+ ];, is important in secretion of catecholamine.