Pathologic responses arising from the pancreatic acinar cell appear to have a central role in initiating
acute pancreatitis. Environmental factors that sensitize the acinar cell to harmful stimuli likely have a critical role in many forms of
pancreatitis, including that induced by
alcohol abuse. Activation of
zymogens within the acinar cell and an inhibition of secretion are critical, but poorly understood, early
pancreatitis events. While there is firm evidence relating
trypsinogen activation to
pancreatitis, the importance of other
zymogens has been less studied. Preliminary studies suggest that
trypsin may be activated by mechanisms that are distinct from other
zymogens. Further, unlike the small intestine, it may not catalyze the activation of other
zymogens. These features could affect strategies aimed at inhibiting
proteases to treat
pancreatitis. Specific intracellular signals are required to activate
pancreatitis pathways in the acinar cell. The most important is
calcium. Recent studies have suggested that
calcium release through specific
calcium channels in the endoplasmic reticulum is the means by which pathological elevations in cytosolic
calcium occur. Although the targets of abnormal calcium signaling are unknown,
calcineurin, a calcium-dependent
phosphatase, may serve such a role. Finally, recent work suggests that an acute
acid load might sensitize the acinar cell to
pancreatitis responses.
Therapies aimed at preventing or reversing the effects of an
acid load on the pancreas may be important for treatment.