Human galanin modulates human colonic motility in vitro. Characterization of structural requirements.

Abstract:

BACKGROUND:Human galanin (hGal) is a 30-residue non-amidated gut-brain peptide that shows considerable sequence divergence compared with galanin (Gal) forms of other species. Conflicting results have been reported with regard to the structural requirements for its modulatory action on gut motility. METHODS:We investigated the effect of human and rat Gal and substituted analogues of Gal on the contractility of longitudinal muscle strips of the human colon in vitro. RESULTS:Both hGal and rGal contracted the preparations in a concentration-dependent and tetrodotoxin-resistant manner without difference in sensitivity. The NH2-terminally truncated peptides hGal (3-30) and rGal (3-29) were inactive, whereas the NH2-terminal fragments, hGal (1-21) and rGal (1-18), remained fully responsive. Single amino acid substitutions at NH2-terminal positions showed divergent results: substitution of Trp2 reduced significantly potency and efficacy, whereas substitutions at positions 1, 3, 4, or 5 did not markedly modify the bioactivity of Gal. Galantide, a high-affinity Gal antagonist in the central nervous system, is a full agonist in human colonic smooth muscle. CONCLUSION:The COOH-terminal part of Gal contributes mainly the receptor-binding affinity of the peptide, whereas the NH2-terminal region is essential for biologic activity.

journal_name

Scand J Gastroenterol

authors

Katsoulis S,Clemens A,Morys-Wortmann C,Schwörer H,Schaube H,Klomp HJ,Fölsch UR,Schmidt WE

doi

10.3109/00365529609006763

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

446-51

issue

5

eissn

0036-5521

issn

1502-7708

journal_volume

31

pub_type

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