Aim: 

Alcohol consumption is thought that is involved in approximately 40% of cases of acute pancreatitis. Here we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca²⁺ signals in mouse pancreatic acinar cells.

Methods: 

Cells were prepared by collagenase treatment followed by mechanical dissociation and loaded with fura-2. Monitorization of changes in fluorescence signals was performed in a fluorescence spectrophotometer.

Results: 

Stimulation of cells with 1 nM CCK-8 lead to an initial increase in cytosolic free calcium concentration ([Ca²⁺]_c) followed by a decrease towards values close to the pre-stimulation level. In the presence of 50mM ethanol, CCK-8 lead to a greater Ca²⁺ mobilization compared to that obtained with CCK-8 alone: The "peak" of CCK-8-evoked Ca²⁺ response, the "steady-state level" reached 5 min after stimulation, the rate of decay of [Ca²⁺]_c towards basal values and the total Ca²⁺ mobilization were significantly affected by ethanol pre-treatment. The sarcoplasmic reticulum Ca²⁺-ATPase (SERCA)-inhibitor, thapsigargin induced an increase in [Ca²⁺]_c due to Ca²⁺ release from intracellular stores. In the presence of 50 mM ethanol, a greater thapsigargin-induced Ca²⁺ response, a slower rate of decay of [Ca²⁺]_c and higher values of [Ca²⁺]_c were observed. A delay or reduced Ca²⁺ extrusion from the cytosol towards the extracellular space by plasma membrane Ca²⁺-ATPase, or into the intracellular stores by SERCA may underlie the effects of ethanol on Ca²⁺ signalling.

Conclusion: 

Our results suggest that ethanol, leading to a delayed or reduced Ca²⁺ extrusion from the cytosol towards the extracellular space or into the cytosolic stores, induce a cytosolic Ca²⁺ overload that could be the basis of alcoholic pancreatitis.

The present study was supported by Junta de Extremadura-FEDER (PRI08A018).