Background and Aims: Peristaltic contraction of the esophagus and relaxation of the lower esophageal sphincter (LES) are mediated by nitric oxide (NO')-producing myenteric nerves, NO synthase immunoreactivity and calcitonin gene-related peptide (CGRP) immunoreactivity colocalize in these nerves. CGRP relaxes the LES and decreases the amplitude of esophageal peristalsis. The aim of this study was to test the hypothesis that CGRP plays a role in nerve-induced responses of the esophagus. Methods: Smooth muscle strips from the LES and the body of the esophagus were stimulated by an electrical field to evoke nerve-mediated responses. Results: CGRP decreased the amplitude and lengthened the latency of the off-response, and it relaxed the LES. Tetrodotoxin did not block the CGRP-induced LES relaxation. The CGRP antagonist CGRP 8-37 inhibited the effects of exogenous CGRP, it increased the amplitude and shortened the latency of the off-response, and it increased the resting tone of the LES. CGRP 8-37 did not inhibit LES relaxation or esophageal contraction. N(ω)-nitro-L-arginine abolished nerve-induced relaxation of the LES muscle and the esophageal off-response but not the relaxation produced by CGRP. Conclusions: These data support the hypothesis that CGRP may decrease the LES basal tone and modulate the timing and amplitude of the esophageal off-responses.
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