The role of calcium in pancreatitis

BACKGROUND/AIMS: A large, sustained increase in acinar [Ca2+](i) may play a key role in the pathogenesis of acute pancreatitis. Many mechanisms which lead to cell damage in vitro and pancreatitis in, vivo, such as free radica ls or supraphysiological cerulein concentrations, cause a rapid increase in [Ca2+](i) in pancreatic acinar cells. Little is known about why [Ca2+](i) increases in some instances stimulate secretion and in other instances init iate cell death. So far, [Ca2+](i) increases were thought to represent phys iological signals when they occurred as oscillations at the single cell lev el. METHODOLOGY: This paper reviews recent literature and our own original rese arch about the role of calcium in the function of pancreatic acinar cells a nd the development of pancreatitis. RESULTS: Recent studies showed that exposure of acinar cells' to free radic als not only caused a bulk increase in [Ca2+](i) but also resulted in calci um oscillations which had a lower frequency than, but similar amplitude to oscillations occurring after physiological stimuli. The absolute increase i n [Ca2+](i) did not definitely determine the cellular response. Instead, th e duration of [Ca2+](i) increase may have been more important. In contrast to previous belief of a direct relationship between [Ca2+](i) oscillations and exocytosis, recent results show that radicals can induce [Ca2+](i) osci llations which do not exert exocytosis but inhibit the secretory response t o physiological stimuli. Further experiments showed that the [Ca2+](i) rele ase caused by radicals originates from thapsigargin-insensitive, ryanodine- sensitive stores. CONCLUSIONS: The origin and duration of [Ca2+](i) increases rather than the ir extent or oscillatory nature, determine whether the cell will secrete or die. An abnormal [Ca2+](i) increase can trigger trypsin activation, acinar cell damage and acute pancreatitis. This hypothesis is supported by studie s which show that calcium chelators inhibit radical-induced trypsin activat ion as well as cell necrosis and apoptosis. Thus, an inhibition of patholog ical [Ca2+](i) release may have a therapeutic potential.