Sistema Gastrointestinal e Digestivo

Abstrato

Role of Calcitonin Gene-related Peptide in Gastric Motility Function: Animal and Human Studies

Shaquana Y. Clark, Pandu R. Gangula

Diabetes is one of the leading causes of gastroparesis. Gastroparesis is a state of partial gastric paralysis where gastric emptying is delayed due to slower or faster gastric motility. Over the years, many other distinct causes of gastroparesis have emerged, including collagen-related vascular diseases and Parkinson’s disease. Calcitonin gene-related peptide, or CGRP, a potent smooth muscle relaxant, is a 37-amino acid neuropeptide found in the gastrointestinal system that has been shown to slow gastric emptying in healthy rodents. Regulation of its synthesis and release from neurons is achieved in part by activation of the transient receptor potential vanilloid subtype 1 (TRPV1). Regulation of its function is achieved by binding to its own receptor, a complex of the Calcitonin Receptorlike Receptor (CRLR) and Receptor Activity Modifying Protein 1 (RAMP1). In the gastrointestinal system, CGRP regulates the release of somatostatin, also known as Growth Hormone Inhibiting Hormone, or GHIH. Somatostatin functions to inhibit the release of gastric acid thus, demonstrating a possible indirect role of CGRP in the pathogenesis of gastroparesis. Cells present in the gastrointestinal system include mucosal cells, submucosal cells, myenteric neuronal cells, and others. CGRP is localized in the gastric mucosa and the myenteric plexus. The neurons present in the enteric or myenteric nervous system play a vital role in gastric motility functions. CGRP is released from the inhibitory neurons in the enteric or myenteric nervous system. Both serum and gastric CGRP have been found to be decreased in diabetes, but it is not known whether these decreases play a role in the pathogenesis of gastroparesis in diabetic/idiopathic patients. The present review provides information about CGRP, its functions, and its possible roles in gastroparesis. The findings presented can be a great asset to the medical community in directing future research for possible causes and developing treatments for gastroparesis.