Calcitonin Gene-Related Peptide (CGRP) modulates cholinergic neurotransmission in the small intestine of man, pig and guinea-pig via presynaptic CGRP receptors

The effect of calcitonin gene-related peptide (CGRP) on the cholinergically mediated twitch contraction in longitudinal muscle strips of the small intestine (duodenum, jejunum, ileum) of guinea-pig, pig and man was investigated. Independently of the anatomical region, CGRP inhibited the twitch response in the different specimens of all three species by about 40% with similar IC 50 values (1.5–2.4 nmol/l). Only in the guinea-pig small intestine CGRP induced a contraction of the smooth muscle which was sensitive to scopolamine and tetrodotoxin. The electrically evoked [ 3H]acetylcholine release from jejunal longitudinal muscle strips with myenteric plexus attached of the guinea-pig, which were incubated with [ 3H]choline, was concentration-dependently inhibited by CGRP. A direct relaxant effect of CGRP on smooth muscle tone of carbachol precontracted preparations was only observed in specimens of the guinea-pig. In conclusion, presynaptic inhibitory CGRP receptors on cholinergic neurones modulate the release of acetylcholine in different parts of the small intestine.