Cholecystokinin (CCK) Regulation of Pancreatic Acinar Cells: Physiological Actions and Signal Transduction Mechanisms

Pancreatic acinar cells synthesize and secrete about 20 digestive enzymes and ancillary proteins with the processes that match the supply of these enzymes to their need in digestion being regulated by a number of hormones (CCK, secretin and insulin), neurotransmitters (acetylcholine and VIP) and growth factors (EGF and IGF). Of these regulators, one of the most important and best studied is the gastrointestinal hormone, cholecystokinin (CCK). Furthermore, the acinar cell has become a model for seven transmembrane, heterotrimeric G protein coupled receptors to regulate multiple processes by distinct signal transduction cascades. In this review, we briefly describe the chemistry and physiology of CCK and then consider the major physiological effects of CCK on pancreatic acinar cells. The majority of the review is devoted to the physiologic signaling pathways activated by CCK receptors and heterotrimeric G proteins and the functions they affect. The pathways covered include the traditional second messenger pathways PLC-IP3-Ca2+, DAG-PKC, and AC-cAMP-PKA/EPAC that primarily relate to secretion. Then there are the protein-protein interaction pathways Akt-mTOR-S6K, the three major MAPK pathways (ERK, JNK, and p38 MAPK), and Ca2+-calcineurin-NFAT pathways that primarily regulate non-secretory processes including biosynthesis and growth, and several miscellaneous pathways that include the Rho family small G proteins, PKD, FAK, and Src that may regulate both secretory and nonsecretory processes but are not as well understood. (C) 2019 American Physiological Society.