RELAXANT EFFECT OF XENIN ON RAT ILEUM IS MEDIATED BY APAMIN-SENSITIVENEUROTENSIN-TYPE RECEPTORS

The action of xenin, a novel 25-residue peptide of the neurotensin (NT )/xenopsin family, was investigated in isolated rat ileal muscle strip s and in dispersed longitudinal smooth muscle cells of rat small intes tine in vitro. Xenin relaxes KCl-precontracted ileal strips dose depen dently (1 nM-3 mu M). The order of potency of the investigated peptide s was as follows: xenopsin = NT = xenin > neuromedin N. Kinetensin was inactive. Tetrodotoxin, hexamethonium, tetraethylammonium, 4-aminopyr idine, and N-G-nitro-L-arginine did not influence the relaxant effects of xenin or NT, whereas the K+ channel blocker apamin nearly abolishe d their effects. Desensitization against one of the peptides or blocka de of NT receptors by SR-48692 prevented the effect of xenin and NT. S tructure-activity experiments revealed that the COOH-terminal part of the molecules of xenin and NT is essential for biological activity. Ex periments with isolated dispersed smooth muscle cells and binding stud ies 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 recept or.