Abstract
Intracellular activation of trypsinogen was considered to be the key mechanism responsible for the initiation of acute pancreatitis. However, accumulating evidence has suggested that activation of trypsinogen, activation of NF-κB, impairment of autophagy, oxidative stress, ER stress, and derangement in calcium signaling occur simultaneously in the onset of acute pancreatitis. The precise mechanism of acute pancreatitis is still obscure and there is no specific treatment. The exocrine secretion of pancreatic enzymes is regulated by cytoplasmic calcium concentration ([Ca2+]i). The signals of acetylcholine and cholecystokinin through their receptors, localized on the basal plasma membrane, induce a calcium spike in the apical area of the acinar cell, resulting in the secretion of pancreatic enzymes. Pathological signals by hyperstimulation of secretagogue, bile and alcohol metabolites, cause sustained and global [Ca2+]i elevation, followed by trypsinogen activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. When we inhibited such a prolonged and abnormal [Ca2+]i elevation using calcium sensor (calmodulin), specific Ca2+ chelator, and CRAC channel blocker, premature enzyme activation, vacuole formation and acinar cell damage were reduced. In this section, physiological and pathological calcium signaling and the onset of acute pancreatitis are discussed.
