Abstract

It is well established that interactions of neuropeptides with several cell types at various parts of the intestine are critically involved in intestinal pathophysiology. Among them, neurotensin has been identified as an important mediator in the development and progress of several gastrointestinal functions and disease conditions, exerting its effects by interacting with specific receptors that exert direct and indirect effects on nerves, epithelial cells, and cells of the immune and inflammatory systems. This review summarizes our recent understanding on the participation of neurotensin in the physiology and pathophysiology of the small and large intestine, and discusses various mechanisms that could be involved in these actions.

Keywords: Neurotensin; GI tract; motility; Inflammation; Signaling

Abbreviations: NT, neurotensin; NTR, NT receptor; GI, gastrointestinal; GPCR, G protein-coupled receptors; IL-8, interleukin-8; NF-κB, nuclear factor-κB; EGFR, epidermal growth factor receptor; IBD, inflammatory bowel diseases

Article Outline

1. Expression of neurotensin and its receptor in the gastrointestinal (GI) tract

1.1. Expression of neurotensin in the GI tract

1.2. NT receptors and their expression in the GI tract

2. Role of NT in motility of GI tract

2.1. Fat is a major and potent stimulus of NT release in intestine

2.2. NT inhibits secretion and motility in the upper GI tract

2.3. Effect of NT in colonic motility

2.4. NT stimulates chloride secretion in animal and human colon

3. NT and intestinal inflammation

3.1. Interaction of NT with mast cells

3.2. Interaction of NT with leukocytes

3.3. Interaction of NT with endothelial cells

3.4. NT interacts with intestinal epithelial cells

3.5. Pathophysiological role of NT and NTS1 in acute intestinal inflammation

3.6. Cellular mechanism of NT-mediated proinflammatory intestinal effects

4. NT promotes healing in chronic colitis

5. Role of NT in colonic responses to stress

6. Summary

References