Calcium is involved in both positive and negative modulation of the secretory system for ANP

The calcium dependence of the atrial natriuretic peptide (ANP) secretory system is controversial. Some studies clearly support a stimulatory role, whereas others favor an inhibitory role for calcium in this endocrine system. We demonstrate that calcium is involved in both a positive modulatory role and a negative modulatory role, thereby providing some explanation for the seemingly irreconcilable findings previously published. The negative modulatory role performed by calcium is evident during basal secretion, whereas the positive modulatory role is especially evident in the sustained phase of the secretory response to stimulation. Furthermore, we demonstrate the calcium dependence of processing of the prohormone to the mature circulating form in a cell culture system. This supports the concept that processing is a function of the atrial myocyte rather than of the mesenchymal cells of the atrium. We have demonstrated previously that calcium is important for packaging of the prohormone into secretory granules. Together these findings support a multifaceted role for calcium in the regulation of the secretory apparatus for ANP.