Receptor biology and signal transduction in pancreatic acinar cells

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.

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. Ca 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 Ca-releasing messengers, cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate, in initiating and coordinating Ca signaling. Progress has also been made in determining the roles of specific organelles in Ca release. Ca 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.

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.