CELL-VOLUME CHANGES MODULATE CHOLECYSTOKININ-STIMULATED AND CARBACHOL-STIMULATED AMYLASE RELEASE IN ISOLATED RAT PANCREATIC ACINI

Background & Aims: Changes in cell volume have been recently identifie d as modulators of cell function and gene expression. This study evalu ated the regulation of exocrine secretion by pancreatic acini on the b asis of changes in cell hydration. Methods: Acini were exposed to hypo tonicity or hypertonicity. The effects of corresponding changes in cel l volume on various cell functions were analyzed. Results: Hypertonici ty and hypotonicity caused a stepwise cell shrinkage and swelling, res pectively. Cell shrinkage decreased and cell swelling increased amylas e secretion stimulated by cholecystokinin (CCK) and carbachol but not by secretin. Changes in cell volume did not alter basal or CCK-stimula ted calcium concentrations or CCK-stimulated inositol triphosphate gen eration. The regulation of secretion by cell volume is not mediated vi a changes in CCK receptor binding or protein kinase C. The increase of amylase release caused by hypotonicity was completely inhibited by cy tochalasin B, colchicine, and genistein. Hypotonicity as well as CCK c aused activation of mitogen-activated protein kinases. Conclusions: Ch anges 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 involv e the cytoskeleton, protein phosphorylation, and activation of mitogen -activated protein kinases.