Pathobiology of acute pancreatitis: focus on intracellular calcium and calmodulin.

Abstract

The exocrine pancreas synthesizes all the enzymes needed for intestinal breakdown of proteins, fats, and carbohydrates in our diet. Unfortunately, the proteases needed for the digestion of the meat we eat can, if inappropriately activated inside the acinar cells, also digest the pancreas itself as well as the surrounding tissues, which is what happens in the sometimes fatal human disease acute pancreatitis. The disease is currently untreatable, but significant progress has recently been made in understanding the fundamental processes initiating the pathological changes underlying pancreatic autodigestion. It is now clear that intracellular trypsin activation-a crucial step in pathogenesis-is due to excessive release of Ca(2+) from intracellular stores, principally via two types of inositol trisphosphate receptor. The unexpected recent discovery of an intrinsic protective mechanism caused by intracellular calmodulin and, specifically, the finding that this protective effect can be boosted by a membrane-permeable Ca(2+)-like peptide are promising.