Ethanol consumption as inductor of pancreatitis

Figure 3 Putative mechanisms of action of ethanol on pancreatic acinar cells physiology. EtOH may, either itself or through its metabolites, sensitize the exocrine pancreas to physiological agonists. The point of action of ethanol may be at the R on the cell surface or intracellular. A stimulated Ca²⁺ release from the ER and a reduction in Ca²⁺ extrusion from the cytosol by the SERCA and/or the PMCA, will lead to accumulation of Ca²⁺ within the cytosol. This may lead to an overproduction of ROS which, in turn, will augment cytosolic Ca²⁺ accumulation, apart from other cellular effects. Cytosolic Ca²⁺ overload, together with ROS generation, may inhibit exocytosis of digestive enzymes (Z) that will accumulate inside the cell. Intracellular trapped digestive enzymes may be activated, and may initiate the autodigestion of the gland, establishing an inflammatory process. On the other hand, ethanol and/or its metabolites can activate intracellular routes for inflammation and/or cell proliferation, contributing to the impairment of cell function and to an uncontrolled cell growth. ER: Endoplasmic reticulum; SERCA: Sarco-endoplasmic reticulum Ca²⁺-ATPase; PMCA: Plasma membrane Ca²⁺-ATPase; IP₃R: Inositol 1,4,5-trisphosphate.