Protein kinase C in the pancreatic acinar cell

Authors

  • Fred Gorelick,

    1. Department of Internal Medicine, Connecticut VA Healthcare and
    2. Yale University, West Haven, Connecticut, and
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  • Stephen Pandol,

    1. VA Greater Los Angeles, Los Angeles, California, USA
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  • Edwin Thrower

    Corresponding author
    1. Department of Internal Medicine, Connecticut VA Healthcare and
    2. Yale University, West Haven, Connecticut, and
      Dr Edwin Thrower, GI Research Laboratory, Building 4, VA Healthcare System CT, Yale University School of Medicine, 950 Campbell Avenue, West Haven, CT 06516, USA. Email: edwin.thrower@yale.edu
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Dr Edwin Thrower, GI Research Laboratory, Building 4, VA Healthcare System CT, Yale University School of Medicine, 950 Campbell Avenue, West Haven, CT 06516, USA. Email: edwin.thrower@yale.edu

Abstract

Pathological activation of selective signaling molecules within the pancreatic acinar cell mediates the development of acute pancreatitis. Some of the key early acinar cell events include activation of proteases, inhibition of apical secretion, and elaboration of inflammatory mediators. Previous studies have shown that supraphysiological concentrations of cholecystokinin (CCK) that can cause pancreatitis in vivo, also initiate these pathological responses in dispersed groups of acinar cells (acini). Protein kinase C (PKC) regulates many cellular events and a role for this family of signaling molecules has been described in some of the pathological responses of pancreatitis. Notably, ethanol can activate specific PKC isoforms and sensitize the acinar cells to the pathological effects of CCK. Our preliminary studies in isolated pancreatic acini and a cell-free reconstitution system suggest that PKC can mediate protease activation in the acinar cell. These findings may be relevant to the pathogenesis of pancreatitis from alcohol and other etiologies.

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