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Involvement of calcitonin gene-related peptide in rat experimental colitis
1Pharmacology Department, Malesci Pharmaceuticals, Florence, Italy.
Abstract:
This study investigated the role of capsaicin-sensitive fibers on trinitrobenzensulphonic acid (TNB)-induced colitis in rats. Capsaicin pretreatment (164 + 164 mumol/kg sc in 2 days) produced an increase of damaged area and colon wet weight at 24 h and 1 week after the challenge. On the other hand, acute stimulation of sensory nerves by local application of capsaicin (1.2-60 mumol/kg) as well as exogenous administration of CGRP (2.6-26.3 nmol/kg sc) ameliorated the lesions and reduced the increase of colon weight in TNB-colitis. The protective effect of acute capsaicin (7.7 mumol/kg) was transient and lost in capsaicin-desensitized animals, showing its specificity and the likely participation of acute release of peptides in this mechanism. Moreover, development of TNB colitis was associated with a selective decrease in tissue CGRP-like immunoreactivity. These findings provide evidence that capsaicin-sensitive nerves, probably via the release of protective neurotransmitters such as CGRP, play a defensive role in colitis.