Effects of calcitonin gene-related peptide on opossum esophageal smooth muscle.
OBJECTIVE
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 omega-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.
Uc
A
A
Department of Pediatrics, University of Iowa College of Medicine, Iowa City, USA.
Murray
J A
JA
Conklin
J L
JL
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004943:Esophagogastric Junction / Q000187:drug effects / Q000502:physiology; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009197:Myenteric Plexus / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D009893:Opossums; D010446:Peptide Fragments / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D015740:Calcitonin Gene-Related Peptide