The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas

This review deals with the roles of calcium and ATP in the control of the normal functions of the different cell types in the exocrine pancreas as well as the roles of these molecules in the pathophysiology of Acute Pancreatitis. Repetitive rises in the local cytosolic calcium ion concentration in the apical part of the acinar cells do not only activate exocytosis but also, via an increase in the intra-mitochondrial calcium ion concentration, stimulate the ATP formation that is needed to fuel the energy-requiring secretion process. However, intracellular calcium overload, resulting in a global sustained elevation of the cytosolic calcium ion concentration, has the opposite effect of decreasing mitochondrial ATP production and this initiates processes that lead to the necrotic destruction of the cells. In the last few years it has become possible to image calcium signalling events simultaneously in acinar, stellate and immune cells in intact lobules of the exocrine pancreas. This has disclosed processes by which these cells interact with each other, particularly in relation to the initiation and development of Acute Pancreatitis. By unravelling the molecular mechanisms underlying this disease, several promising therapeutic intervention sites have been identified. This provides hope that we may soon be able to effectively treat this often fatal disease