Site of action of galanin in the cholinergic transmission of guinea pig small intestine.

The mode and site of action of galanin were examined in the guinea pig small intestine. Galanin (3 x 10(-9)-10(-7) M) inhibited the twitch contractions of longitudinally and circularly oriented muscle strips mediated by the stimulation of cholinergic neurons, but not the contractions mediated by direct stimulation of smooth muscle cells with carbachol. Galanin (3 x 10(-9)-10(-7) M) inhibited both the electrically stimulated and the tetrodotoxin-resistant high K+ (40 mM)-induced increase of [3H]acetylcholine outflow from the ileal strips preloaded with [3H]choline, in a concentration dependent fashion. The inhibitory effect of galanin was antagonized by galantide and produced self-desensitization. The spontaneous and stimulated outflow of [3H]noradrenaline and [3H]gamma-aminobutyric acid were not affected by galanin even at 10(-7) M. Thus, galanin inhibits the motility of guinea pig ileum by inhibition of acetylcholine release from the enteric cholinergic neurons. Galanin may act on the specific receptor located on soma-dendritic regions and nerve terminals of cholinergic neurons.