MAGNESIUM HOMEOSTASIS AND ITS ROLE IN THE EXOCRINE PANCREAS IN HEALTHAND DISEASE

Magnesium (Mg2+) is the most abundant intracellular divalent cation in cells and it is involved in several physiological and biochemical pro cesses during cellular regulation. During the past two decades new ana lytic methods have been developed to measure accurately small amounts of Mg2+ in cell in health and diseased states. As a result a body of k nowledge about the biological role of Mg2+ has been energed in a numbe r of different cell types and systems of the body, Research in our lab oratories over the past 4-5 years has focussed on the relationship bet ween calcium (Ca2+) and Mg2+ signalling during the stimulus-secretion- coupling process and the molecular mechanism of Mg2+ transport in panc reatic acinar cells. This review is concerned mainly with the progress of Mg2+ biology in relation to exocrine pancreatic function in health and disease. Mg2+ is distributed mainly around the rough microsomes a nd in zymogen granules of acinar cells. It is released in pancreatic j uice during basal conditions and upon stimulation. A modification of e xtracellular Mg2+ [Mg2+](0) can have profound effect on secretagogue-e voked pancreatic juice secretion. Elevated [Mg2+](0) inhibited secreta gogue-evoked-secretory responses whereas low [Mg2+](0) has the opposit e effect. Mg2+ can elecit its regulatory effect on pancreatic juice se cretion by modulating the mobilization of cellular Ca2+. The divalent cation exerts its effect on Ca2+ homeostasis by regulating the metabol ism of inositol trisphosphate IP3) and Ca2+-ATPase in the endoplasmic reticulum (ER) and plasma membrane resulting in the release of Ca2+ fr om the ER and its influx into cells. Since Mg2+ can regulate Ca2+ tran sport then it is equally important in understanding the homeostasis of Mg2+ in pancreatic acinar cells. Mg2+ uptake into acinar cells is ass ociated with membrane potential changes whereas secretagogue-evoked Mg 2+ efflux is inhibited by either cyclic AMP, nitro-l-arginine (NLA) or lanthanum chloride but stimulated by protein kinase C and Ca2+ influx factor (CIF). In these respects drugs which can regulare Mg2+ transpo rt by elevating its intracellular concentration may have clinical rele vance for the treatment of pancreatitis. In conclusion, the results pr esented in this review strongly support an important modulatory role o f Mg2+ in the control of exocrine pancreatic function. Research studie s are now concentrating on the role of dietary intake of Mg2+ on the a etiology and prevention of pancreatitis.