Changes in mitochondrial activity evoked by cholecystokinin in isolated mouse pancreatic acinar cells.
In the present study, we have employed confocal laser scanning microscopy to investigate the effect that stimulation of mouse pancreatic acinar cells with the secretagogue cholecystokinin (CCK) has on mitochondrial activity. We have monitored changes in cytosolic as well as mitochondrial Ca2+ concentrations, mitochondrial membrane potential and FAD autofluorescence by loading the cells with fluo-3, rhod-2 or JC-1, respectively. Our results show that stimulation of cells with cholecystokinin led to release of Ca2+ from intracellular stores that then accumulated into mitochondria. In the presence of the hormone a depolarization of mitochondrial membrane potential was observed, which partially recovered; in addition a transient increase in FAD autofluorescence could be observed. Similarly, treatment of cells with thapsigargin induced increases in mitochondrial Ca2+ and FAD autofluorescence, and depolarized mitochondria. Pretreament of cells with thapsigargin blocked cholecystokinin-evoked changes. Similar results were obtained when the cells were incubated in the presence of rotenone, which blocks the mitochondrial electron transport chain. Our findings are consistent with changes in mitochondrial activity in response to stimulation of pancreatic acinar cells with cholecystokinin. Following stimulation, mitochondria take up Ca2+ that could in turn activate the mitochondrial machinery that may match the energy supply necessary for the cell function during secretion, suggesting that Ca2+ can act as a regulator of mitochondrial activity.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005456:Fluorescent Dyes; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D012844:Sincalide / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology
D005456:Fluorescent Dyes; D005182:Flavin-Adenine Dinucleotide; D019284:Thapsigargin; D012844:Sincalide; D002118:Calcium