PancreasReceptor biology and signal transduction in pancreatic acinar cellsBi, Yana; Williams, John A.a bAuthor Information a Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA; and b Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA Correspondence to John A. Williams, MD, PhD, Molecular and Integrative Physiology, 7744 Medical Science II, University of Michigan, Ann Arbor, MI 48109-0622, USA, Tel: 734 764 4376; fax: 734 936 8813; e-mail: [email protected] Current Opinion in Gastroenterology: September 2004 - Volume 20 - Issue 5 - p 427-434 Buy SDC Abstract Purpose of review Secretagogue receptors and their intracellular signaling pathways regulate pancreatic physiology and may be altered in pathophysiology. Therefore, understanding of the continued progress into their nature and function is relevant to both biology and disease. Recent findings The major secretagogue receptors on acinar cells include those binding cholecystokinin and acetylcholine, whereas secretin receptors regulate duct cells. Two physical models of the cholecystokinin receptor and ligand binding have been proposed through extensive structure-activity studies. Receptor oligomerization has been described for both cholecystokinin and secretin receptors. Ca2+ plays a central role in the control of digestive enzyme secretion and is largely mobilized from intracellular stores. Inositol trisphosphate has been joined by two other Ca2+-releasing messengers, cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate, in initiating and coordinating Ca2+ signaling. Progress has also been made in determining the roles of specific organelles in Ca2+ release. Ca2+ triggers secretion, and knowledge of the function and regulation of the proteins involved in exocytosis is accumulating. Continuing advances have also been made in understanding the signaling pathways regulating protein synthesis and growth in adult pancreas. The protein kinase mammalian target of rapamycin and its downstream targets play a central role in protein synthesis, whereas the protein phosphatase calcineurin was recently reported to regulate pancreatic growth. Other signaling molecules include the MAP kinases, PKCs, cytoplasmic tyrosine kinases, and nitric oxide. Summary The current findings reviewed here are illuminating the structure and function of receptors on pancreatic acinar and duct cells and the multiple intracellular signaling pathways that they initiate. Understanding of these mechanisms is contributing to knowledge of normal pancreatic functions and alterations in disease such as pancreatitis and pancreatic cancer. © 2004 Lippincott Williams & Wilkins, Inc.