Ca2+ signalling and pancreatitis: effects of alcohol, bile and coffee.

Ca2+ is a universal intracellular messenger that controls a wide range of cellular processes. In pancreatic acinar cells, acetylcholine and cholecystokinin regulate secretion via generation of repetitive local cytosolic Ca2+ signals in the apical pole. Bile acids and non-oxidative alcohol metabolites can elicit abnormal cytosolic Ca2+ signals that are global and sustained and result in necrosis. Necrosis results from excessive loss of Ca2+ from the endoplasmic reticulum, which is mediated by Ca2+ release through specific channels and inhibition of Ca2+ pumps in intracellular stores, followed by entry of extracellular Ca2+. Reduction of the cellular ATP level has a major role in this process. These abnormal Ca2+ signals, which can be inhibited by caffeine, explain how excessive alcohol intake and biliary disease cause acute pancreatitis, an often-fatal human disease in which the pancreas digests itself and its surroundings.