title: Protective roles of alpha-calcitonin and beta-calcitonin gene-related peptide in spontaneous and experimentally induced colitis.
abstract: 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 alphaCGRP or betaCGRP 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 betaCGRP show no obvious alterations in CGRP immunoreactivity in the gut, accompanied by an increase in alphaCGRP messenger RNA expression, suggesting an adaptive mechanism to compensate for the lack of betaCGRP. These data demonstrate that both alphaCGRP and betaCGRP play a protective role in the generation of spontaneous colitis, supporting a role for both extrinsic and intrinsic CGRP-containing neurons.
authors.affiliation: Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232-8548, USA.
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Thompson
authors.forename: Mary K
authors.initials: MK
authors.lastname: Washington
authors.forename: Usha
authors.initials: U
authors.lastname: Kurre
authors.forename: Minati
authors.initials: M
authors.lastname: Singh
authors.forename: Elizabeth Y
authors.initials: EY
authors.lastname: Rula
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Emeson
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics* / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D012313:RNA; D016264:Dextran Sulfate; D015740:Calcitonin Gene-Related Peptide