Effects of Nitroprusside and Nicorandil on Catecholamine Secretion and Calcium Mobilization in Cultured Bovine Adrenal Chromaffin Cells

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Abstract
The effects of nitroprusside and nicorandil on catecholamine secretion and free intracellular Ca2+ ([Ca2+]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 [Ca2+]i-dependent secretory process. These effects were compared with those of nifedipine, a typical voltage-dependent Ca2+ channel blocker. Carbachol produced a rapid increase followed by a sustained increase of [Ca2+]i (Ca2+ transient) in cultured bovine adrenal chromaffin cells. Both nitroprusside and nicorandil accelerated the decrease in [Ca2+]i without changing the peak values of the initial [Ca2+]i increase of Ca2+ transient. These drugs, however, did not affect carbachol-induced catecholamine secretion, suggesting that secretion is related to the initial [Ca2+]i increase and not to a late sustained [Ca2+]i increases. However, nifedipine reduced the peak and duration of carbachol-induced [Ca2+]i increases and decreased the secretion of catecholamines. Diethylamine/NO complex, an NO donor, and dibutyryl-cGMP produced similar changes in Ca2+ 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 Ca2+ transient, especially the initial increase in [Ca2+]i, is important in secretion of catecholamine.