Role of N-terminal active sites of galanin in neurally evoked circular muscle contractions in the guinea-pig ileum.

Synthetic galanin-related peptides and several galanin-(1-15)ol analogs were used to examine structure-function relationships of the N-terminal active site of galanin in more detail, using the guinea-pig ileum. The synthetic peptides examined showed their inhibitory activity on the neurally evoked circular muscle contractions with the following order of potency: rat, human and tuna galanin, galanin-(1-15)ol and [D-Trp8]galanin-(1-15)ol > N alpha-acetylated galanin-(2-15)ol, [Ala6,D-Trp8]galanin-(1-15)ol, galanin-(1-15) > tuna galanin-(1-15), [D-Ala8]galanin-(1-15)ol, N alpha-acetylated galanin-(1-15)ol. In contrast, [D-Thr6]galanin-(1-15)ol, [D-Tyr9]galanin-(1-15)ol and [D-Trp9]galanin-(1-15)ol were ineffective and showed no antagonistic activities to galanin. These results suggest that the L-configuration at positions 6 and 9 seems to be important for the inhibitory action of galanin on the neurally evoked guinea-pig circular muscle contractions.