Receptor-mediated signal transduction pathways and the... : Current Opinion in Gastroenterology (original) (raw)

Pancreas: Edited by Chung Owyang

Receptor-mediated signal transduction pathways and the regulation of pancreatic acinar cell function

Departments of Molecular & Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

Correspondence to John A. Williams, MD, PhD, Molecular & Integrative Physiology, University of Michigan, 7744 Medical Science II, 1301 E. Catherine Street, Ann Arbor, MI 48109-5622, USA Tel: +1 734 764 4376; fax: +1 734 936 8813; e-mail: [email protected]

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

Understanding the mechanisms that regulate pancreatic acinar cell function is contributing to our knowledge of normal pancreatic function and alterations in diseases such as pancreatitis and pancreatic cancer.