Protective Roles of α-Calcitonin and β-Calcitonin Gene-Related Peptide in Spontaneous and Experimentally Induced Colitis

Calcitonin gene-related peptide (CGRP) is thought to be involved in the regulation of gastric and mesenteric blood flow, in the control of gastric acid secretion and in the modulation of intestinal motility, yet the precise physiological roles of CGRP remain to be elucidated. To further examine the role(s) of CGRP in gastrointestinal function, we examined mutant mice lacking αCGRP or βCGRP expression. Mutant mice did not demonstrate any overt phenotypic changes, yet exhibited a spontaneous, adult-onset colitis and increased colonic damage using a dextran sulfate sodium model of experimental colitis. Surprisingly, mice lacking βCGRP show no obvious alterations in CGRP immunoreactivity in the gut, accompanied by an increase in αCGRP messenger RNA expression, suggesting an adaptive mechanism to compensate for the lack of βCGRP. These data demonstrate that both αCGRP and βCGRP play a protective role in the generation of spontaneous colitis, supporting a role for both extrinsic and intrinsic CGRP-containing neurons.