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.
Kakuyama
H
H
Laboratory of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Japan.
Kuwahara
A
A
Mochizuki
T
T
Hoshino
M
M
Yanaihara
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004558:Electric Stimulation; D019004:Galanin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D005769:Gastrointestinal Motility; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D051381:Rats; D013329:Structure-Activity Relationship; D014413:Tuna
D019004:Galanin