In pancreatic acinar cells, normal enzyme secretion is controlled by local calcium spikes in the apical granular pole (Petersen, O.H.: Cell Calcium 38, 171–200, 2005). Bile acids and non-oxidative alcohol metabolites can elicit global and sustained cytosolic calcium signals due to depletion of endoplasmic reticulum calcium stores and subsequent activation of calcium entry. This results in acinar cell necrosis (Petersen, O.H. & Sutton, R.: Trends Pharmacol. Sci (TIPS) in press (February Issue 2006). With regard to the action of the non-oxidative alcohol metabolites (fatty acid ethyl esters and fatty acids), there are two separate mechanisms working in parallel: Activation of IP3 receptors and inhibition of mitochondrial ATP synthesis (Criddle, D.N., Murphy, J., Fistetto, G., Barrow, S., Tepikin, A.V., Neoptolemos, J.P., Sutton, R. & Petersen, O.H.: Gastroenterology in press (March Issue 2006). Coffee has some protective effect against alcoholic pancreatitis, probably due to the inhibitory effect of caffeine on IP3 activation of IP3 receptors (Wakui, M., Osipchuk, Y. & Petersen, O.H. Cell 63, 1025–1032, 1990)