Asynchronous impairment of calcium homoeostasis in different acinar cells after pancreatic duct obstruction in rat.
Current evidence suggests that alterations within acinar cells are responsible for the development of acute pancreatitis. After inducing acute pancreatitis in rats by pancreatic duct obstruction, we analysed, using flow cytometry, the progressive changes in cytosolic Ca2+ concentrations in individual acinar cells from the earliest stages to 48 h after obstruction to investigate whether parallel alterations in the homoeostasis of Ca2+ could be defined in the different acinar cells throughout the evolution of pancreatitis. Morphological alterations of the pancreas, related to the severity of the disease at different stages, were observed by electron microscopy. Hyperamylasaemia and progressively more severe alterations, such as vacuolization, dilatation of endoplasmic reticulum, accumulation of zymogen granules and reorientation towards basolateral membrane, were observed during the first 12 h after pancreatic obstruction. A significant increase in cytosolic Ca2+ concentration was measured at these stages in a particular type of acinar cells (R1) differentiated by flow cytometry with low forward scatter (FSC), whereas another representative group of cells (R2) with higher FSC values were able to maintain resting cytosolic Ca2+ concentrations up to 24 h after obstruction. Longer periods of pancreatic duct obstruction induced disturbances in Ca2+ homoeostasis in all acinar cells. A similar increase in cytosolic Ca2+ load was reached in both R1 and R2 cells when acute pancreatitis was completely developed. In conclusion, the homoeostasis of Ca2+ in acinar cells is asynchronously impaired during the development of acute pancreatitis; cells with higher FSC (R2) appear to be more resistant than R1 cells.
Uruñuela
Aránzazu
A
Department of Physiology and Pharmacology, Edificio Departamental, Campus Miguel de Unamuno s/n, 37007 Salamanca, Spain.
Manso
Manuel A
MA
de la Mano
Ana Ma
AM
Sevillano
Sara
S
Orfao
Alberto
A
de Dios
Isabel
I
D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005434:Flow Cytometry; D006706:Homeostasis; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000648:ultrastructure; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D002118:Calcium