Ca2+ signalling and pancreatitis: effects of alcohol, bile and coffee.
Ca2+ is a universal intracellular messenger that controls a wide range of cellular processes. In pancreatic acinar cells, acetylcholine and cholecystokinin regulate secretion via generation of repetitive local cytosolic Ca2+ signals in the apical pole. Bile acids and non-oxidative alcohol metabolites can elicit abnormal cytosolic Ca2+ signals that are global and sustained and result in necrosis. Necrosis results from excessive loss of Ca2+ from the endoplasmic reticulum, which is mediated by Ca2+ release through specific channels and inhibition of Ca2+ pumps in intracellular stores, followed by entry of extracellular Ca2+. Reduction of the cellular ATP level has a major role in this process. These abnormal Ca2+ signals, which can be inhibited by caffeine, explain how excessive alcohol intake and biliary disease cause acute pancreatitis, an often-fatal human disease in which the pancreas digests itself and its surroundings.
Petersen
Ole H
OH
MRC Group, Physiological Laboratory and Division of Surgery and Oncology, University of Liverpool, Liverpool L69 3BX, UK. o.h.petersen@liv.ac.uk
Sutton
Robert
R
D000818:Animals; D001646:Bile / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003069:Coffee; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D010195:Pancreatitis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D011493:Protein Kinase C / Q000502:physiology
D002492:Central Nervous System Depressants; D003069:Coffee; D000431:Ethanol; D011493:Protein Kinase C