Pathophysiology of alcohol-induced pancreatitis.
Excessive ethanol consumption is a common risk factor for acute and chronic pancreatitis. Ethanol could lead to the onset of pancreatitis in a number of ways; the most recently discovered is its effect on intrapancreatic digestive enzyme activation, by either sensitizing acinar cells to pathologic stimuli or stimulating the release of a secretagogue (cholecystokinin) from duodenal I cells. Recent advances in cell biologic and molecular techniques have permitted us to address the intracellular events involved in digestive enzyme activation in a manner that was previously considered impossible. Investigations that used these novel techniques found that (a) trypsin is, in contrast to its role in the small intestine, not necessarily involved in the premature intracellular activation of other digestive proteases such as proelastase; (b) trypsinogen does not autoactivate intracellularly but is instead largely activated by the lysosomal hydrolase cathepsin B; and (c) the role of trypsin in the intrapancreatic protease cascade is most likely one that involves the degradation, rather than the activation, of active digestive proteases including trypsin itself. These studies, as well as investigations that have addressed the role of mutant trypsin in the disease onset of hereditary pancreatitis, suggest that trypsin may not be critical for triggering pancreatitis but might have a protective role against the action of some of the other digestive proteases. While the specific role of different digestive enzymes in initiating pancreatitis is still a matter of debate and the topic of ongoing investigations, experimental evidence suggests that ethanol can directly interfere with the processes involved in digestive zymogen activation.
Department of Medicine A, Ernst-Moritz-Arndt Universität, Greifswald, Germany. lerch@uni-greifswald.de
Markus M
MM
Lerch
Elke
E
Albrecht
Manuel
M
Ruthenbürger
Julia
J
Mayerle
Walter
W
Halangk
Burkhard
B
Krüger
D000079:Acetaldehyde / Q000494:pharmacology; D002401:Cathepsin B / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000139:chemically induced / Q000503:physiopathology*; D014357:Trypsin / Q000378:metabolism
D014357:Trypsin; D002401:Cathepsin B; D000079:Acetaldehyde