Role of Calcitonin Gene-Related Peptide in Gastric Mucosal Defence and Healing

Calcitonin gene-related peptide (CGRP) is a polypeptide produced by alternative processing of calcitonin gene transcripts and is endowed with important systemic physiological effects. The recent characterization of its receptor and the discovery of stable antagonists has addressed them in the indication migraine. Beside this, several studies have been focused on role of CGRP at gastric level. CGRP is considered a marker of afferent fibers in the upper gastrointestinal tract being almost completely depleted following treatment with the selective neurotoxin capsaicin that targets these fibers via transient receptor potential vanilloid of type-1. The exogenous administration of the peptide was able to afford protection against experimental ulcers induced by an increase in gastric secretion. The use of CGRP knockout mice has let to characterize the endogenous role of CGRP showing that the local release of this neuropeptide protects from ethanol injury and favours ulcer healing. Decreased levels of gastric CGRP-like immunoreactivity (li) were observed during acetic acid-, cysteamine-, concentrated ethanol- or water immersion stress-ulcers. Restoration of CGRP-li was found in animals bearing ulcers in healing status and delayed healing in mice knockout to CGRP. CGRP was able to release somatostatin from gastric D cells but its main effects on the stomach homeostasis rely on local vasodilator action during increased acidback diffusion.