Stimulation of calcitonin gene-related peptide release through targeting capsaicin receptor: a potential strategy for gastric mucosal protection

Abstract

Calcitonin gene-related peptide (CGRP) is a predominant neurotransmitter from capsaicin-sensitive sensory nerves, which are widely distributed in the gastrointestinal system. These sensory nerves are reported to be involved in the protection of gastric mucosa against damage by various stimuli, and CGRP is a potential mediator in this process. In addition to increase in gastric mucosal blood flow, the beneficial effects of CGRP on gastric mucosa include inhibition of gastric acid secretion, prevention of cellular apoptosis and oxidative injury. The synthesis and release of CGRP is regulated by the capsaicin receptor which is known as transient receptor potential vanilloid subfamily member 1 (TRPV1) and the agonists of TRPV1 have the potential for gastric mucosal protection. So far, multiple TRPV1 agonists, including capsaicin, capsiate, anandamide and rutaecarpine are reported to exert beneficial effects on gastric mucosal injury induced by various stimuli. Therefore, the TRPV1/CGRP pathway represents a novel target for therapeutic intervention in human gastric mucosal injury.