Abstract
Recently we demonstrated that sensory denervation with the neurotoxin capsaicin worsened the inflammation in an acute and chronic model of experimental colitis, which suggests a protective role of sensory nerve fibers during gut inflammation. Because we could demonstrate that sensory neuropeptides like Calcitonin gene-related peptide (CGRP) and substance P (SP) are released from sensory nerve fibers during intestinal inflammation, both are strong candidates as mediators for the protective effect of sensory neurons. In this study we investigate the role of CGRP and SP during experimental colitis in the rat by use of receptor antagonists against CGRP (CGRP8–37, 1 μg/h continuous subcutaneous infusion), SP (RP67580, a NK-1 receptor antagonist, 3 mg/kg i.p.) and an immunoneutralizing CGRP-antibody. A mild colitis was induced by a rectal enema containing trinitrobenzenesulfonic acid. The severity of inflammation increased markedly after 7 days in the CGRP receptor antagonist and CGRP-antibody group compared with the vehicle group as determined by a macroscopic damage score (10.4 ± 1.2 and 9.6 ± 1.6 vs. 6.2 ± 2.1) by a histologic ulceration score (82 ± 8% and 73 ± 6% vs. 42 ± 23%) and by myeloperoxidase activity (19.2 ± 6.8 and 18.1 ± 5.9 vs. 8.6 ± 5.3 U/mg tissue protein), respectively. Treatment with the specific SP receptor antagonist did not significantly alter the severity of colitis at 7 days compared with the control group. These data suggest that CGRP exerts mucosal protection during chronic experimental colitis.
Footnotes
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Send reprint requests to: Max Reinshagen M.D., Department of Medicine I, University of Ulm, Robert Kochstr. 8, 89081 Ulm, Germany. E-mail: max.reinshagen{at}medizin.uni-ulm.de
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↵1 This study was supported by the Deutsche Forschungsgemeinschaft (Re 789/2–1).
- Abbreviations:
- CGRP
- Calcitonin Gene-related peptide
- SP
- Substance P
- TNB
- Trinitrobenzenesulfonic acid
- MPO
- myeloperoxidase
- mAb
- monoclonal antibody
- NO
- nitric oxide
- KLH
- keyhole limpet hemocyanin
- PB
- Phosphate Buffer
- Received October 13, 1997.
- Accepted April 17, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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