Cell volume changes modulate cholecystokinin- and carbachol-stimulated amylase release in isolated rat pancreatic acini

Background & Aims: Changes in cell volume have been recently identified as modulators of cell function and gene expression. This study evaluated the regulation of exocrine secretion by pancreatic acini on the basis of changes in cell hydration. Methods: Acini were exposed to hypotonicity or hypertonicity. The effects of corresponding changes in cell volume on various cell functions were analyzed. Results: Hypertonicity and hypotonicity caused a stepwise cell shrinkage and swelling, respectively. Cell shrinkage decreased and cell swelling increased amylase secretion stimulated by cholecystokinin (CCK) and carbachol but not by secretin. Changes in cell volume did not alter basal or CCK-stimulated calcium concentrations or CCK-stimulated inositol triphosphate generation. The regulation of secretion by cell volume is not mediated via changes in CCK receptor binding or protein kinase C. The increase of amylase release caused by hypotonicity was completely inhibited by cytochalasin B, colchicine, and genistein. Hypotonicity as well as CCK caused activation of mitogen-activated protein kinases. Conclusions: Changes in cell volume regulate exocrine secretion of pancreatic acini. The effects were found only for secretagogues that act via the calcium/inositol-trisphosphate pathway. However, the mechanisms involved are located at luminal parts of the signal-transduction cascade and involve the cytoskeleton, protein phosphorylation, and activation of mitogen-activated protein kinases.