title: Ethanol augments elevated-[Ca2+]C induced trypsin activation in pancreatic acinar zymogen granules.
abstract: It has been long recognized that significant percentage of patients with acute pancreatitis often presents with a history of excessive alcohol consumption; however, the patho-physiological effect of ethanol on acute pancreatitis remains poorly understood. Abnormally elevated cytosolic Ca2+ ([Ca2+]C) has been found to be a shared phenomenon in acute pancreatitis that could induce trypsin premature activation. Here, we present the effects of ethanol to sensitize zymogen granules (ZGs) of pancreas acinar cells to elevated [Ca2+]C leading to zymogen premature activation that could result in acute pancreatitis. The pH fluctuations ([pH]G), Ca2+ concentration ([Ca2+]G), and premature trypsin activation inside the ZGs were monitored directly with specific fluorescence indicators. Our results showed that ethanol could act directly on ZGs and cause ZGs more receptive to elevated [Ca2+]C that could induce premature activation of zymogen (trypsin). This alcohol-induced effect is concentration dependent and strongly influenced by the surrounding [Ca2+]C. The K+ channels on ZGs membranes are required in the sensitization process. Our observations provide a mechanistic understanding of the role of ethanol in the initiation phase of alcoholic pancreatitis.
authors.affiliation: College of Engineering, Florida State University, Tallahassee, FL 32310, USA.
authors.forename: Yong-Xue
authors.initials: YX
authors.lastname: Ding
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chin
mesh_terms: D000818:Animals; D002118:Calcium / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism*; D014357:Trypsin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000431:Ethanol; D014357:Trypsin; D002118:Calcium