Calcitonin gene-related peptide action on intestinal circular muscle

Isolated segments of the guinea pig small intestine were used to examine the effect of calcitonin gene-related peptide (CGRP) on the motor activity of the circular muscle. CGRP (0.3-30 nM) initiated phasic contractions of the circular muscle due to stimulation of cholinergic neurons. Peristalsis, however, was inhibited by CGRP. A further analysis of this effect showed that CGRP had no inhibitory influence on the main, cholinergic, pathway of the ascending enteric reflex (AER) contraction, whereas the hexamethonium- and atropine-resistant pathways of the AER were blocked. The inhibition of the atropine-resistant AER resulted from an action of CGRP on nerves and, since it was antagonized by apamin, might be explained by a CGRP-induced activation of enteric inhibitory neurons. The direct relaxant action of CGRP on the longitudinal muscle was not affected by apamin. These findings indicate a heterogeneity and topical selectivity in the motor actions of CGRP on the gut and suggest that this peptide, when released from nerve endings within the intestine, plays a specific role in the regulation of intestinal motility.