Intracellular magnesium: transport and regulation in epithelial secretory cells

The mechanisms of magnesium (Mg2+) transport, the regulation of intracellular Mg2+ concentrations and the relationship between Mg2+ and Ca2+ signaling during the stimulus-secretion coupling process in pancreatic acinar cells and other secretory epithelia are reviewed in this article. Our results demonstrate the existence of a Na+- and ATP-dependent transport system for Mg2+ extrusion from Mg2+-loaded cells. Moreover, employing such different techniques as spectrofluorimetry and atomic absorbance spectroscopy to measure intracellular free magnesium concentration [Mg2+]i from magfura-2-loaded acini and acinar cells and Mg2+ content in effluent samples from perfused pancreatic segments, respectively, confirm that secretagogues such as acetylcholine (ACh) and cholecystokinin-octapeptide (CCK-8) can evoke marked and significant extrusion of Mg2+ which is closely associated with the mobilization of intracellular calcium. These effects may be modulated by different mediators including cAMP, Protein Kinase C and nitric oxide/cGMP. This reduction in [Mg2+]i seems to be a prerequisite for optimal generation and maintenance of the calcium signal and subsequently, the secretion of enzymes, since an increase in extracellular Mg2+ concentration, [Mg2+]o and an increase in [Mg2+]i inhibit secretagogue-induced secretory responses, an effect exerted through a derangement of the calcium signaling events. In conclusion, the evidence presented in this review strongly supports an important modulatory role of magnesium in the control of secretory epithelial cells function.