AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 1 190-G196, Copyright © 1997 by American Physiological Society
Relaxant effect of xenin on rat ileum is mediated by apamin-sensitive neurotensin-type receptors
A. Clemens, S. Katsoulis, R. Nustede, J. Seebeck, K. Seyfarth, C. Morys-Wortmann, G. E. Feurle, U. R. Folsch and W. E. Schmidt
I. Department of Medicine, University of Kiel, Germany.
The action of xenin, a novel 25-residue peptide of the neurotensin
(NT)/xenopsin family, was investigated in isolated rat ileal muscle strips
and in dispersed longitudinal smooth muscle cells of rat small intestine in
vitro. Xenin relaxes KCl-precontracted ileal strips dose dependently (1
nM-3 microM). The order of potency of the investigated peptides was as
follows: xenopsin = NT = xenin > neuromedin N. Kinetensin was inactive.
Tetrodotoxin, hexamethonium, tetraethylammonium, 4-aminopyridine, and
NG-nitro-L-arginine did not influence the relaxant effects of xenin or NT,
whereas the K+ channel blocker apamin nearly abolished their effects.
Desensitization against one of the peptides or blockade of NT receptors by
SR-48692 prevented the effect of xenin and NT. Structure-activity
experiments revealed that the COOH-terminal part of the molecules of xenin
and NT is essential for biological activity. Experiments with isolated
dispersed smooth muscle cells and binding studies on intestinal smooth
muscle cell membranes confirmed and extended the results obtained with
muscle strips. In conclusion, xenin relaxes rat ileal smooth muscle via a
muscular NT-type apamin-sensitive receptor.
