University of Michigan, Departments of Molecular & Integrative Physiology and Internal Medicine (Gastroenterology), Ann Arbor, Michigan, USA.
Compr Physiol. 2019 Mar 14;9(2):535-564. doi: 10.1002/cphy.c180014.
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-Ca , 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 Ca -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. © 2019 American Physiological Society. Compr Physiol 9:535-564, 2019.
胰腺腺泡细胞合成并分泌大约 20 种消化酶和辅助蛋白，这些酶的分泌过程与它们在消化中的需求相匹配，这一过程受到许多激素（胆囊收缩素、促胰液素和胰岛素）、神经递质（乙酰胆碱和 VIP）和生长因子（EGF 和 IGF）的调节。在这些调节剂中，最重要和研究最多的之一是胃肠激素胆囊收缩素（CCK）。此外，腺泡细胞已成为七跨膜异三聚体 G 蛋白偶联受体的模型，通过不同的信号转导级联调节多种过程。在这篇综述中，我们简要描述了 CCK 的化学和生理学，然后考虑了 CCK 对胰腺腺泡细胞的主要生理影响。本文的大部分内容致力于描述 CCK 受体和异三聚体 G 蛋白激活的生理信号通路及其影响的功能。所涵盖的途径包括与分泌主要相关的传统第二信使途径 PLC-IP3-Ca 、DAG-PKC 和 AC-cAMP-PKA/EPAC，然后是 Akt-mTOR-S6K 蛋白-蛋白相互作用途径、三大 MAPK 途径（ERK、JNK 和 p38 MAPK）以及 Ca -calcineurin-NFAT 途径，它们主要调节非分泌过程，包括生物合成和生长，以及几个包括 Rho 家族小 G 蛋白、PKD、FAK 和 Src 的混杂途径，它们可能调节分泌和非分泌过程，但了解得还不够深入。© 2019 美国生理学会。《综合生理学》9:535-564, 2019。
