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Pancreatitis: the neglected duct
  1. Min Goo Lee1,
  2. Shmuel Muallem2
  1. 1
    Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea
  2. 2
    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  1. Dr Shmuel Muallem, Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9040, USA; Schmuel.muallem{at}utsouthwestern.edu

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Acute and chronic pancreatitis are multifactorial diseases that involve inflammation of the pancreas, generation of toxic mediators and mistargeting of digestive enzymes that eventually result in destruction of the parenchyma.1 Because acinar cells contain the harmful mistargeted digestive enzymes and the extensive damage occurs in acinar cells in all forms and models of pancreatitis, research into the triggers and causes of pancreatitis have been focused on acinar cells.1 It is now well established that aberrant Ca2+ signalling leading to a sustained and prolonged increase in free cytoplasmic Ca2+ concentration ([Ca2+]i) is the nodal point in pancreatitis that perturbs many functions of acinar cells, leading to their destruction.

While undoubtedly destruction of acinar cells is the terminal step in pancreatitis, the duct is likely to play a crucial role in protecting the pancreas, and when this protection is compromised pancreatitis ensues. The central function of the pancreatic duct is the secretion of most of the fluid in the pancreatic juice and the coupled absorption of Cl and secretion of HCO3 to generate juice containing as much as 140 mM HCO3.2 The fluid is required to wash the harmful digestive enzymes away from the acinar lumen and ensure their exit from the pancreas. The HCO3 has several functions. Besides titrating part of the gastric acid in the duodenum, alkalinisation of the pancreatic juice by HCO3 prevents premature activation of digestive enzymes. Equally importantly, as a chaotropic ion HCO3 facilitates the solubilisation of divalent ions and of macromolecules, including the digestive enzymes and mucins, in the pancreatic juice.

The critical importance of fluid and HCO3 secretion by the pancreatic duct is evident from the inhibition of fluid and HCO3– …

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