Can pancreatitis be treated by inhibiting Ca2+ signaling?
Ionized calcium (Ca2+) has long been known to be a major controller of cell function including pancreatic acinar cell secretion; in fact, research on pancreatic acinar cells in the 1980’s was instrumental in establishing the mechanisms by which sequestered calcium is released into the cytoplasm to act as an intracellular messenger in response to hormones and neurotransmitters (1). In acinar cells this signaling consists of transient Ca2+ elevations in the apical pole of the cell that triggers exocytosis of zymogen granules (2). Hyperstimulation of acinar cells especially by CCK led to a large single peak of Ca2+ followed by a plateau of elevated calcium. Since hyperstimulation by the CCK analog cerulein has long been known to induce experimental pancreatitis (3), it was a logical step forward to show using isolated pancreatic acini that a high level of intracellular Ca2+ was associated with and probably caused premature trypsin activation, cell vacuolization, and necrosis which are considered the in vitro equivalent of acute pancreatitis (AP) (4-6).