Digestive Diseases and Sciences

, Volume 53, Issue 1, pp 229–241

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

  • Brent J. Thompson
  • Mary K. Washington
  • Usha Kurre
  • Minati Singh
  • Elizabeth Y. Rula
  • Ronald B. Emeson
Original Paper

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 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.

Keywords

Myenteric plexus Lymphoid hyperplasia Gene targeting Dextran sodium sulfate Adaptive compensation Neuropeptide 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Brent J. Thompson
    • 1
  • Mary K. Washington
    • 2
  • Usha Kurre
    • 3
  • Minati Singh
    • 4
  • Elizabeth Y. Rula
    • 5
  • Ronald B. Emeson
    • 1
    • 6
    • 7
  1. 1.Center for Molecular NeuroscienceVanderbilt University School of MedicineNashvilleUSA
  2. 2.Department of PathologyVanderbilt University School of MedicineNashvilleUSA
  3. 3.Department of PharmacologyVanderbilt University School of MedicineNashvilleUSA
  4. 4.Department of PsychologyUniversity of IowaIowa CityUSA
  5. 5.Department of PharmacologyVanderbilt University School of MedicineNashvilleUSA
  6. 6.Department of PharmacologyVanderbilt University School of MedicineNashvilleUSA
  7. 7.Department of Molecular Physiology & BiophysicsVanderbilt University School of MedicineNashvilleUSA

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