Mechanism of alcohol-related acute pancreatitis identified
MEDICAL RESEARCH COUNCIL MEDIA RELEASE
MRC/33/09
UK scientists have identified the critical proteins involved in alcohol-related pancreatitis making it much easier to search for a treatment. Medical Research Council Professor, Ole Petersen FRS, and his co-workers at the University of Liverpool, have worked in collaboration with Professor Katsuhiko Mikoshiba and his group at RIKEN Brain Science Institute in Japan.
Pancreatitis, which is often associated with alcohol abuse, is an important and often fatal inflammatory disease of the pancreas, which affects approximately 100 - 300 people per 100,000 in the population and is of increasing incidence in both the UK and Japan. The toxic effects of alcohol are mediated through calcium release in the cells of the pancreas, which activates digestive enzymes and damages the cell.
The MRC-supported researchers have now identified the importance of a specific calcium store in the development of pancreatitis and found that calcium ions move out of this store into the cell water through special calcium channels, namely IP3 receptors of types 2 and 3.
Professor Ole Petersen said: “There is currently no specific drug treatment for pancreatitis. However, now that this research has identified the critical proteins responsible for the excessive calcium release, which is where the problem begins, it will be much easier to search systematically for specific chemicals for the treatment of acute pancreatitis.
“The most important result of this new joint UK-Japanese collaboration is that by deleting the genes for these special calcium channels, it is possible markedly to reduce the excessive toxic calcium release and the consequent dangerous intracellular enzyme activation, which is induced by the alcohol metabolites.”
The toxic effects of alcohol on the pancreas are principally brought about by the products of alcohol and fat (called fatty acid ethyl esters) which are generated in the pancreas when oxygen levels in the organ are low. These products trigger an excessive increase in the calcium ion concentration in the cell water inside the pancreatic cells, which in turn activates digestive enzymes inside the cells. The primary cause of the excessive build-up in calcium ion concentration is the movement of calcium ions from calcium stores surrounded by their own membranes inside the cell into the cell water.
The pancreatic digestive enzymes are normally only activated after having been secreted into the gut, where they are important for the normal digestion process, but when activated prematurely inside the cells, they digest the pancreas itself and its surroundings causing severe damage, which is often fatal.
For further information and to arrange an interview with Professor Ole Petersen and colleagues on this project, please contact Nicola Osmond-Evans in the MRC Press Office on 020 7670 5138 or press.office@headoffice.mrc.ac.uk
Notes to editors:
- Dr. Ole Petersen is one of the world’s leading physiologists working on signal-transduction mechanisms in pancreatic acinar cells. He discovered local apical signals as important regulators of acinar secretion. His work has been widely recognized, most importantly by his election as Fellow of The Royal Society in 2000 and more recently last year, when Queen Elizabeth II appointed him Commander of the Order of the British Empire (CBE) for ‘Services to Science’.
- Original Research paper: Pancreatic protease activation by alcohol metabolite depends on Ca2+ release via acid store IP3 receptors, will be published on 16 June 2009 in the online Early Edition of `Proceedings of the National Academy of Sciences of the United States of America`(PNAS).
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