Molecular basis for pancreatitis

Abstract

Purpose of review. Recent studies on pancreatic acinar cell function have led to a more detailed understanding of the signal transduction mechanisms regulating digestive enzyme synthesis and secretion as well as pancreatic growth. This review identifies and puts into context these recent studies, which further understanding in these areas. Recent findings Receptors present on acinar cells, particularly those for cholecystokinin and secretin, have been better characterized as to the molecular nature of the ligand-receptor interaction. Other reports have described the receptors for natriuretic peptides and fibroblast growth factor on acini. Intracellular Ca2+ signaling remains at the center of stimulus secretion coupling and its regulation by inositol 1,4,5-trisphosphate, nicotinic acid adenine dinucleotide phosphate and cyclic ADP-ribose has been further defined. Work downstream of intracellular mediators has focused on molecular mechanisms of exocytosis particularly involving small G proteins, soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and cytoskeletal proteins. Considerable progress has been made defining the complex in acinar cells and its regulation. In addition to secretion, recent studies have further defined the regulation of pancreatic growth both in adaptive regulation to diet and hormones, particularly cholecystokinin, and in the regeneration that occurs after pancreatitis or partial pancreatectomy. This regulation involves calcineurin-nuclear factor of activated T cells, mammalian target of rapamycin, mitogen-activated protein kinase, Notch signaling pathways as well as various tyrosine kinases. Summary. The implications of the last year's findings are widespread. Improved animal models of acute pancreatitis and chronic pancreatitis will be critical for performing pilot studies of therapy. A greater understanding of genetic factors and pain responses could lead to potential treatments. This review will first discuss issues related to acute pancreatitis, and then conclude with studies most relevant to chronic disease. © 2008 Wolters Kluwer Health \ Lippincott Williams & Wilkins.