Calcium signaling of pancreatic acinar cells in the pathogenesis of pancreatitis

Abstract

Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca²⁺) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca²⁺ overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca²⁺ signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca²⁺ elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca²⁺ from stores in the intracellular endoplasmic reticulum and/or increased Ca²⁺ entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca²⁺ by the sarco/endoplasmic reticulum Ca²⁺-activated ATPase and plasma membrane Ca²⁺-ATPase pumps, which contribute to Ca²⁺ overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca²⁺ signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca²⁺ signals in the pathogenesis of pancreatitis.

Keywords: Pancreatitis; Calcium signaling; Pancreatic acinar cells; Overload; Cell injury

Core tip: Calcium (Ca²⁺) overload is crucial in the pathogenesis of pancreatitis, which results in trypsin activation, vacuolization and necrosis. Such cell injury results from increased Ca²⁺ released from intracellular endoplasmic reticulum Ca²⁺ stores, increased Ca²⁺ entry through the plasma membrane and Ca²⁺ pump defects. Current findings have provided further insight into the roles and mechanisms of Ca²⁺ overload in pancreatitis. The lack of specific treatments is a stimulus for ongoing research. This review summarizes recent advances in our understanding of Ca²⁺ signaling in the pathogenesis of pancreatitis, and discusses how research has guided our search for potential therapeutic targets.