Increased calcium influx in the presence of ethanol in mouse pancreatic acinar cells.
The effects of alcohol on Ca(2+) signalling remains poorly understood. Here we have investigated the effects of acute ethanol exposure on Ca(2+) influx in mouse pancreatic acinar cells. Cells were loaded with fura-2 and the changes in fluorescence were monitored by spectrofluorimetry and imaging analysis. Stimulation of cells with 20 pM cholecystokinin evoked an oscillatory pattern in [Ca(2+)](c), both in the presence and in the absence of extracellular Ca(2+). Stimulation of cells with cholecystokinin in the presence of 50 mM ethanol led to a transformation of physiological oscillations into a single transient increase in [Ca(2+)](c). This effect was observed when Ca(2+) was present in the extracellular medium, and did not appear in its absence. Addition of 1 mM CaCl(2) to the extracellular medium, following release of Ca(2+) from intracellular stores by stimulation of cells with 1 nM cholecystokinin or 1 microM thapsigargin in the absence of extracellular Ca(2+), was followed by an increase in [Ca(2+)](c). Ca(2+) influx was increased in the presence of 50 mM ethanol. The anti-oxidant cinnamtannin B-1 (10 microM) or inhibition of alcohol dehydrogenase by 4-MP (1 mM), significantly reduced Ca(2+) influx evoked by cholecystokinin in the presence of ethanol. In summary, intoxicating concentrations of ethanol may lead to over stimulation of pancreatic acinar cells by cholecystokinin. This might be partially explained by the generation of reactive oxygen species and an increased Ca(2+) entry in the presence of ethanol. Potentially ethanol might lead to Ca(2+) overload, which is a common pathological precursor that is implicated in pancreatitis.
Del Castillo-Vaquero
Angel
A
Department of Physiology (Cell Physiology Research Group), University of Extremadura, Cáceres, Spain.
Salido
Ginés M
GM
González
Antonio
A
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D051379:Mice; D046790:Pancreas, Exocrine / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012844:Sincalide / Q000378:metabolism; D019284:Thapsigargin / Q000378:metabolism
D017382:Reactive Oxygen Species; D000431:Ethanol; D019284:Thapsigargin; D000426:Alcohol Dehydrogenase; D012844:Sincalide; D002118:Calcium